Abstract

Ethanol exposure to the fetus during pregnancy can result in fetal alcohol spectrum disorders (FASD). These disorders vary in severity, can affect multiple organ systems, and can lead to lifelong disabilities. Damage to the central nervous system (CNS) is common in FASD, and can result in altered behavior and cognition. The incidence of FASD is alarmingly high, resulting in significant personal and societal costs. There are no cures for FASD. Alcohol can directly alter the function of neurons in the developing CNS. In addition, ethanol can alter the function of CNS glial cells including microglia and astrocytes which normally maintain homeostasis in the CNS. These glial cells can function as resident immune cells in the CNS to protect against pathogens and other insults. However, activation of glia can also damage CNS cells and lead to aberrant CNS function. Ethanol exposure to the developing brain can result in the activation of glia and neuroinflammation, which may contribute to the pathology associated with FASD. This suggests that anti-inflammatory agents may be effective in the treatment of FASD.


Authors

Kane, Cynthia J. M.;  Drew, Paul D.

Publons users who've claimed - I am an author

No Publons users have claimed this paper.

  • pre-publication peer review (FINAL ROUND)
    Decision Letter
    2020/09/05

    05-Sep-2020

    Dear Dr Drew:

    Thank you for submitting your manuscript "Neuroinflammatory Contribution of Microglia and Astrocytes in Fetal Alcohol Spectrum Disorders" by Kane, Cynthia ; Drew, Paul.

    You will be pleased to know that your manuscript has been accepted for publication. Thank you for submitting this excellent work to our journal.

    In the coming weeks, the Production Department will contact you regarding a copyright transfer agreement and they will then send an electronic proof file of your article to you for your review and approval.

    Please note that your article cannot be published until the publisher has received the appropriate signed license agreement. Within the next few days, the corresponding author will receive an email from Wiley’s Author Services asking them to log in. There, they will be presented with the appropriate license for completion. Additional information can be found at https://authorservices.wiley.com/author-resources/Journal-Authors/licensing-open-access/index.html

    Would you be interested in publishing your proven experimental method as a detailed step-by-step protocol? Current Protocols in Neuroscience welcomes proposals from prospective authors to disseminate their experimental methodology in the rapidly evolving field of neuroscience. Please submit your proposal here: https://currentprotocols.onlinelibrary.wiley.com/hub/submitaproposal

    Congratulations on your results, and thank you for choosing the Journal of Neuroscience Research for publishing your work. I hope you will consider us for the publication of your future manuscripts.

    Sincerely,

    Dr Alex Marshall
    Associate Editor, Journal of Neuroscience Research

    Dr Cristina Ghiani
    Editor-in-Chief, Journal of Neuroscience Research

    NIH GRANTEES: All NIH authors should also be aware that Wiley-Blackwell will submit manuscripts to the NIH Manuscript Submission system automatically. After their accepted manuscript files have been posted by Wiley-Blackwell to the NIH Manuscript Submission system, the corresponding author will receive an e-mail request from PubMed Central asking them to approve the upload for display on the PubMed Central system. Authors will need to provide approval to complete the process of deposition to PubMed Central. This is a requirement of their grant/affiliation.

    P.S. You can help your research get the attention it deserves! Check out Wiley’s Promotion Guide for best-practice recommendations for promoting your work at www.wileyauthors.com/maximize.

    Decision letter by
    Cite this decision letter
    Author Response
    2020/09/03

    We changed the Reference style to APA as requested.



    Cite this author response
  • pre-publication peer review (ROUND 2)
    Decision Letter
    2020/08/30

    30-Aug-2020

    Dear Dr Drew:

    We are pleased to inform you that your manuscript has been accepted pending one minor modification:
    JNR uses a Name-Year system (i.e. CSE system) in the main text, and the APA style of reference citation.Please revise the manuscript according to the authors' guidelines, which can found at the following website: https://onlinelibrary.wiley.com/page/journal/10974547/homepage/forauthors.html

    We ask that you return your manuscript within 15 days. Please explain in your cover letter how you have changed the present version. If you require longer than 15 days to make the revisions, please contact Dr Cristina Ghiani (cghiani@mednet.ucla.edu).You can submit your revised manuscript directly by clicking on the following link: PLEASE NOTE: This is a two-step process. After clicking on the link, you will be directed to a webpage to confirm.

    https://mc.manuscriptcentral.com/jnr?URL_MASK=aa25f4d4e6be4031a77d87af06e5953f

    Thank you again for your submission to the Journal of Neuroscience Research; we look forward to reading your revised manuscript.

    Best Wishes,

    Dr Alex Marshall
    Associate Editor, Journal of Neuroscience Research

    Dr Cristina Ghiani
    Editor-in-Chief, Journal of Neuroscience Research

    Reviewer: 2

    Comments to the Author
    The authors have addressed the previous concerns.

    Reviewer: 1

    Comments to the Author
    All concerns addressed

    Reviewer: 3

    Comments to the Author
    The authors' revisions have satisfied this reviewer

    *IMPORTANT: Instructions and checklists follow*
    When finalized, please upload your complete revised manuscript onto our website, preferably as a word document. Please ensure to upload a ‘marked’ version of your manuscript along with a ‘clean’ version. The ‘marked’ version should contain all the changes (revised text and any other modification) made to the manuscript clearly shown using a red bold font. The clean version should have no red or marked sentences, strike-through words, or comments in margins. Kindly avoid submitting a document with tracked changes. Figures must be uploaded separately in .tif or eps format. Please review our submission checklist, which can be found in our author guidelines and also be sure to fill out the Transparent Science Questionnaire attached to this email.

    JNR offers Open Science badges to qualifying authors. For more information please see the “Open Science initiatives” section of our author guidelines. If you would like to apply for one or more of the badges, please complete the included disclosure form and upload it as Supplemental Material Not for Review when submitting your final manuscript files.

    To submit your revised manuscript:
    You have two ways to submit your revision. Either click on the link: PLEASE NOTE: This is a two-step process. After clicking on the link, you will be directed to a webpage to confirm. *

    https://mc.manuscriptcentral.com/jnr?URL_MASK=23e34cdac7644b08beacf34e573d50ac or Log on to https://mc.manuscriptcentral.com/jnr using your case-sensitive User ID ((Person not available)).

    For security purposes your password is not listed in this email. If you are unsure of your password you may click the link to set a new password.
    (Person not available)

    Enter the Author Center, where you will find your manuscript title listed under “Manuscripts with Decisions”
    Under “Actions,” click on “Create a Revision”. Your manuscript number has been appended to denote a revision.
    *Follow the prompts and replace existing files with revised ones, as necessary.

    If you encounter any troubles in submitting your revised manuscript, please contact Dr Cristina Ghiani (cghiani@mednet.ucla.edu) or click on Get Help Now at the top right of any ScholarOne Manuscripts screen.

    Decision letter by
    Cite this decision letter
    Reviewer report
    2020/08/21

    The authors' revisions have satisfied this reviewer

    Reviewed by
    Cite this review
    Reviewer report
    2020/08/11

    All concerns addressed

    Reviewed by
    Cite this review
    Reviewer report
    2020/07/28

    The authors have addressed the previous concerns.

    Reviewed by
    Cite this review
    Author Response
    2020/07/27

    Point-by-point Response to Reviewer Comments

    Reviewer: 1

    Comments to the Author

    This is a nice review article by Kane and Drew. It is well written and presents most of the literature in the field. Although likely not available at the time of writing, 2 very recent papers from the Deak group are relevant (Gano et al., Cytokine; Doremus-Fitzwater et al., Frontiers in Behavioral Neuroscience). Response: We added the two references suggested by the reviewer to the manuscript- page 17

    Minor edits:
    Abstract line 2 – affect not effect. Response: We made this change to the Abstract- page 2.

    P. 7 – oligodendrocytes should be separate paragraph (also on p.10). Response: We made the section focusing on oligodendrocytes a separate paragraph, page 7.

    Define OPC at first use. Response: We defined OPC as oligodendrocyte precursor cells when first used, page 5.

    On p.12, the sentence “Microglia exhibited an activated morphology, and levels of the pro-inflammatory cytokines IL-1β and TNF-α, and chemokine CCL2, were elevated in animals treated with ethanol in all three brain regions” should be changed to “Microglia exhibited an activated morphology, and levels of the pro-inflammatory cytokines IL-1β and TNF-α, and chemokine CCL2, were elevated in all three brain regions in animals treated with ethanol.” Response: We changed this sentence to match the suggestion of the reviewer, page 12.

    P.12. line 31 – what is the definition of “moderate ethanol exposure” and of “severe ethanol exposure”? Response: We define moderate or severe ethanol exposure as the authors did in the original manuscript- by providing the dose of ethanol administered to animals, page 12

    p. 13. Line 14-18 One of the words “postnatal” in this sentence is redundant. Response: We removed the word “postnatal” from the beginning of the sentence, page 13.

    Line 24 – what age(s) is included in “early postnatal rats”. Response: We added the ages of the early postnatal rats (P3-5) to the manuscript, page 13.

    Lines 22-31 – the information on micro-hemhorrages is not integrated. Response: We integrated the information on micro-hemhorrages by emphasizing that the micro-hemhorrages are associated with astrogliosis and microgliosis, a major focus of this section of the review, in the first sentence regarding this topic, page 13.

    p.14 second sentence – does the apoptosis persist into adulthood? Response: We removed the statement that “apoptosis persists into adulthood, page 14.

    Reviewer: 2

    Comments to the Author
    This is an interesting and well-written review that will be of broad interest to the JNR readership.

    Minor comments:

    1. The authors should define OPC with its first usage. Response: We defined OPC on first usage, page 5.

    2. Pg 22, ln18- should be "there" remains, not their remains. Response: We made the change suggested by the reviewer, page 21.

    Reviewer: 3

    Comments to the Author
    Review of “The Role of Glia and Neuroinflammation in Fetal Alcohol Spectrum Disorders”

    This is an interesting review on the role of astrocytes and microglia in neuroinflammation in fetal alcohol spectrum disorders. It’s a well-written review but would benefit from certain modifications as discussed below:

    1. The Title is a little misleading given the manuscript. The emphasis on the role of Glia in the title gives the impression that “Glia” in general will be the focus but this is not true as a disproportionate amount of the time of the review is given to microglia (MG) and astrocytes (AS). This reviewer recommends that the title mirror the content of the manuscript and the term “glia” be replaced with “MG and AS”. Response: We changed the title to match that suggested by the reviewer in #2 below.

    2. Also regarding the title, the emphasis on “Glia” in the title also give the impression that that’s the subject matter of focus. This is true in the first third of the manuscript but in the second two-thirds, the focus seems to be on neuroinflammation rather than AS or MG because the authors do not often discuss the cellular source responsible for the inflammatory changes. This, this reviewer recommends that the title be altered to highlight neuroinflammation as the central focus with MG and AS as contributors to that focus. A title like the following will be more appropriate for the manuscript: “Neuroinflammatory contributions of MG and AS in FASD”. Response: We changed the title to match that suggested by the reviewer, page 1.

    3. In the discussion of glia that begins at the bottom of page 4, oligodendrocyte precursor cells (OPCs) should be included in the list of glia. Response: OPCs are defined on first usage as oligodendrocyte precursor cells, page 5.

    4. In the first paragraph of page 5, there is a disproportionate focus on AS over other glia. Perhaps more clarification of MG and Oligodendrocyte (OL) roles as was done for AS should be provided and there should be some discussion on OPCs like for (3) above. Response: There are comments in this section that refer to glia in general. There is also one sentence that is specific to each type of glia- astrocytes, microglia, and oligodendrocytes. We feel that the focus on individual glia is balanced and appropriate, page 5

    5. A few relevant citations are missing. For example:

    a. at the bottom of page 5 and in addition to citation 21, recent transcriptional studies also reveal differences between microglia and infiltrating monocytes e.g. PMID 29643186, 27135602. Response: We added a sentence indicating that recent transcriptional studies indicate differences between microglia and macrophages and added these two citations as suggested by the reviewer, page 5.
    b. Citation #25 in the middle of page 6 is cited to claim that microglia interact with synapses but that study shows no such thing. Therefore, the authors should replace that citation with others including works from Beth Stevens lab, Cornelius Gross’ lab and Junichi Nabekura’s lab. Response: Citation #25 referred to in vivo studies indicating that microglia are highly motile in the first part of the sentence in question. That reference was moved to that point in the sentence. In addition, we added appropriate references from the Stevens, Gross, and Nabekura labs regarding microglia interacting with synapses (Wake et al., 2009; Paolicelli et al., 2011; and Schafer et al., 2012) as suggested by the reviewer, page 6.
    c. On page 7 a discussion of studying microglia in culture during ethanol exposure is provided but the authors fail to discuss the concern about studying microglia in culture, namely that their expression profile changes. See PMID: 29861285. This caveat for at least microglia studies in culture should be provided. Response: The reviewer makes an important point regarding changes in expression profiles when cells are removed from their native environment. The reviewer specifically focused on this concern for microglia, but this is also a concern for other glia as well. Therefore, we have addressed this concern for glia in general in the section which focuses on ethanol effects on cultured glia in vitro. We added a summary paragraph at the end of this section which includes the caveat that transcriptional profile of glia change upon removal from the CNS. We added the reference suggested by the reviewer which focuses on profile changes in microglia (Bennett et al., 2018). We also added an additional reference which discusses changes in transcriptional profiles in vitro in other glia, in addition to microglia (Sloan and Barres, 2018), page 10.
    d. The discussion on page 10 (especially at the top) is littered with claims without sufficient citations to buttress the claims. Similarly the last sentence of page 10 makes a claim on ethanol’s effects on microglial activation but fails to make an appropriate citation. This is also true at the bottom of page 11 where it is claimed that a timepoint in mouse development corresponds to a timepoint in the human context. Response: We added several relevant citations to address the concerns of the reviewer, page 10, 11, and 12.
    e. In the discussion of minocycline the authors should note that minocycline is also thought to possibly affect neurons directly independent of actions on microglia which could complicate the conclusions drawn from thus studies. Please see PMID: 21267407. Response: We added a statement that minocycline can directly protect neurons, in the absence of microglia, in culture and added the Huang et al., 2010 reference suggested by the reviewer, page 20.



    Cite this author response
  • pre-publication peer review (ROUND 1)
    Decision Letter
    2020/07/21

    21-Jul-2020

    Dear Dr Drew:

    Thank you for submitting your manuscript to the Journal of Neuroscience Research. We've now received the reviewer feedback and have appended those reviews below. I'm glad to say that the reviewers are overall very enthusiastic and supportive of the study. They did raise some concerns and made some suggestions for clarification, but I expect that these points should be relatively straightforward to address. If there are any questions or points that are problematic, please feel free to contact me. I am glad to discuss.

    We ask that you return your manuscript within 30 days. Please explain in your cover letter how you have changed the present version. If you require longer than 30 days to make the revisions, please contact Dr Cristina Ghiani (cghiani@mednet.ucla.edu). You can submit your revised manuscript directly by clicking on the following link: PLEASE NOTE: This is a two-step process. After clicking on the link, you will be directed to a webpage to confirm.

    https://mc.manuscriptcentral.com/jnr?URL_MASK=64e8ea2353424548ada593f59ba1cdca

    Thank you again for your submission to the Journal of Neuroscience Research; we look forward to reading your revised manuscript.

    Best Wishes,

    Dr Alex Marshall
    Associate Editor, Journal of Neuroscience Research

    Dr Cristina Ghiani
    Editor-in-Chief, Journal of Neuroscience Research

    Editorial comments:

    Please format the references following the JNR guidelines and add to the paper (after the Discussion and Acknowledgments, immediately before the References) a statement of authors' contributions. The statement must follow the CRediT Taxonomy. You can find examples of such statements in the author guidelines on-line at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-4547/homepage/ForAuthors.html

    Reviewer: 1

    Comments to the Author
    This is a nice review article by Kane and Drew. It is well written and presents most of the literature in the field. Although likely not available at the time of writing, 2 very recent papers from the Deak group are relevant (Gano et al., Cytokine; Doremus-Fitzwater et al., Frontiers in Behavioral Neuroscience).
    Minor edits:
    Abstract line 2 – affect not effect
    P. 7 – oligodendrocytes should be separate paragraph (also on p.10). Define OPC at first use
    On p.12 the sentence “Microglia exhibited an activated morphology, and levels of the pro-inflammatory cytokines IL-1β and TNF-α, and chemokine CCL2, were elevated in animals treated with ethanol in all three brain regions” should be changed to “Microglia exhibited an activated morphology, and levels of the pro-inflammatory cytokines IL-1β and TNF-α, and chemokine CCL2, were elevated in all three brain regions in animals treated with ethanol.”

    P.12. line 31 – what is the definition of “moderate ethanol exposure” and of “severe ethanol exposure”?

    p. 13. Line 14-18 One of the words “postnatal” in this sentence is redundant. Line 24 – what age(s) is included in “early postnatal rats”. Lines 22-31 – the information on micro-hemhorrages is not integrated.

    p.14 second sentence – does the apoptosis persist into adulthood?

    Reviewer: 2

    Comments to the Author
    This is an interesting and well-written review that will be of broad interest to the JNR readership.

    Minor comments:

    1. The authors should define OPC with its first usage

    2. Pg 22, ln18- should be "there" remains, not their remains.

    Reviewer: 3

    Comments to the Author
    Review of “The Role of Glia and Neuroinflammation in Fetal Alcohol Spectrum Disorders”

    This is an interesting review on the role of astrocytes and microglia in neuroinflammation in fetal alcohol spectrum disorders. It’s a well-written review but would benefit from certain modifications as discussed below:

    1. The Title is a little misleading given the manuscript. The emphasis on the role of Glia in the title gives the impression that “Glia” in general will be the focus but this is not true as a disproportionate amount of the time of the review is given to microglia (MG) and astrocytes (AS). This reviewer recommends that the title mirror the content of the manuscript and the term “glia” be replaced with “MG and AS”.

    2. Also regarding the title, the emphasis on “Glia” in the title also give the impression that that’s the subject matter of focus. This is true in the first third of the manuscript but in the second two-thirds, the focus seems to be on neuroinflammation rather than AS or MG because the authors do not often discuss the cellular source responsible for the inflammatory changes. This, this reviewer recommends that the title be altered to highlight neuroinflammation as the central focus with MG and AS as contributors to that focus. A title like the following will be more appropriate for the manuscript: “Neuroinflammatory contributions of MG and AS in FASD”.

    3. In the discussion of glia that begins at the bottom of page 4, oligodendrocyte precursor cells (OPCs) should be included in the list of glia.

    4. In the first paragraph of page 5, there is a disproportionate focus on AS over other glia. Perhaps more clarification of MG and Oligodendrocyte (OL) roles as was done for AS should be provided and there should be some discussion on OPCs like for (3) above.

    5. A few relevant citations are missing. For example:

    a. at the bottom of page 5 and in addition to citation 21, recent transcriptional studies also reveal differences between microglia and infiltrating monocytes e.g. PMID 29643186, 27135602.
    b. Citation #25 in the middle of page 6 is cited to claim that microglia interact with synapses but that study shows no such thing. Therefore, the authors should replace that citation with others including works from Beth Stevens lab, Cornelius Gross’ lab and Junichi Nabekura’s lab.
    c. On page 7 a discussion of studying microglia in culture during ethanol exposure is provided but the authors fail to discuss the concern about studying microglia in culture, namely that their expression profile changes. See PMID: 29861285. This caveat for at least microglia studies in culture should be provided.
    d. The discussion on page 10 (especially at the top) is littered with claims without sufficient citations to buttress the claims. Similarly the last sentence of page 10 makes a claim on ethanol’s effects on microglial activation but fails to make an appropriate citation. This is also true at the bottom of page 11 where it is clamed that a timepoint in mouse development corresponds to a timepoint in the human context.
    e. In the discussion of minocycline the authors should note that minocycline is also thought to possibly affect neurons directly independent of actions on microglia which could complicate the conclusions drawn from thus studies. Please see PMID: 21267407.

    *IMPORTANT: Instructions and checklists follow*
    When finalized, please upload your complete revised manuscript onto our website, preferably as a word document. Please ensure to upload a highlighted version of your manuscript along with the clean version. The highlighted version should highlight the revised text or any other changes made to the manuscript. The clean version should have no highlighted sentences, strike-through words, or comments in margins. Kindly avoid submitting a document with tracked changes. Figures must be uploaded separately in .tif or eps format. Please review our submission checklist, which can be found in our author guidelines and also be sure to fill out the Transparent Science Questionnaire attached to this email.

    JNR offers Open Science badges to qualifying authors. For more information please see the “Open Science initiatives” section of our author guidelines. If you would like to apply for one or more of the badges, please complete the included disclosure form and upload it as Supplemental Material Not for Review when submitting your final manuscript files.

    To submit your revised manuscript:
    You have two ways to submit your revision. Either click on the link: PLEASE NOTE: This is a two-step process. After clicking on the link, you will be directed to a webpage to confirm. *

    https://mc.manuscriptcentral.com/jnr?URL_MASK=ab3a5b66bc29428ab909268ecca093ec or Log on to https://mc.manuscriptcentral.com/jnr using your case-sensitive User ID ((Person not available)).

    For security purposes your password is not listed in this email. If you are unsure of your password you may click the link to set a new password.
    (Person not available)

    Enter the Author Center, where you will find your manuscript title listed under “Manuscripts with Decisions”
    Under “Actions,” click on “Create a Revision”. Your manuscript number has been appended to denote a revision.
    *Follow the prompts and replace existing files with revised ones, as necessary.

    If you encounter any troubles in submitting your revised manuscript, please contact Dr Cristina Ghiani (cghiani@mednet.ucla.edu) or click on Get Help Now at the top right of any ScholarOne Manuscripts screen.

    Decision letter by
    Cite this decision letter
    Reviewer report
    2020/07/21

    Review of “The Role of Glia and Neuroinflammation in Fetal Alcohol Spectrum Disorders”

    This is an interesting review on the role of astrocytes and microglia in neuroinflammation in fetal alcohol spectrum disorders. It’s a well-written review but would benefit from certain modifications as discussed below:

    1. The Title is a little misleading given the manuscript. The emphasis on the role of Glia in the title gives the impression that “Glia” in general will be the focus but this is not true as a disproportionate amount of the time of the review is given to microglia (MG) and astrocytes (AS). This reviewer recommends that the title mirror the content of the manuscript and the term “glia” be replaced with “MG and AS”.

    2. Also regarding the title, the emphasis on “Glia” in the title also give the impression that that’s the subject matter of focus. This is true in the first third of the manuscript but in the second two-thirds, the focus seems to be on neuroinflammation rather than AS or MG because the authors do not often discuss the cellular source responsible for the inflammatory changes. This, this reviewer recommends that the title be altered to highlight neuroinflammation as the central focus with MG and AS as contributors to that focus. A title like the following will be more appropriate for the manuscript: “Neuroinflammatory contributions of MG and AS in FASD”.

    3. In the discussion of glia that begins at the bottom of page 4, oligodendrocyte precursor cells (OPCs) should be included in the list of glia.

    4. In the first paragraph of page 5, there is a disproportionate focus on AS over other glia. Perhaps more clarification of MG and Oligodendrocyte (OL) roles as was done for AS should be provided and there should be some discussion on OPCs like for (3) above.

    5. A few relevant citations are missing. For example:

    a. at the bottom of page 5 and in addition to citation 21, recent transcriptional studies also reveal differences between microglia and infiltrating monocytes e.g. PMID 29643186, 27135602.
    b. Citation #25 in the middle of page 6 is cited to claim that microglia interact with synapses but that study shows no such thing. Therefore, the authors should replace that citation with others including works from Beth Stevens lab, Cornelius Gross’ lab and Junichi Nabekura’s lab.
    c. On page 7 a discussion of studying microglia in culture during ethanol exposure is provided but the authors fail to discuss the concern about studying microglia in culture, namely that their expression profile changes. See PMID: 29861285. This caveat for at least microglia studies in culture should be provided.
    d. The discussion on page 10 (especially at the top) is littered with claims without sufficient citations to buttress the claims. Similarly the last sentence of page 10 makes a claim on ethanol’s effects on microglial activation but fails to make an appropriate citation. This is also true at the bottom of page 11 where it is clamed that a timepoint in mouse development corresponds to a timepoint in the human context.
    e. In the discussion of minocycline the authors should note that minocycline is also thought to possibly affect neurons directly independent of actions on microglia which could complicate the conclusions drawn from thus studies. Please see PMID: 21267407.

    Reviewed by
    Cite this review
    Reviewer report
    2020/07/03

    This is an interesting and well-written review that will be of broad interest to the JNR readership.

    Minor comments:

    1. The authors should define OPC with its first usage

    2. Pg 22, ln18- should be "there" remains, not their remains.

    Reviewed by
    Cite this review
    Reviewer report
    2020/07/02

    This is a nice review article by Kane and Drew. It is well written and presents most of the literature in the field. Although likely not available at the time of writing, 2 very recent papers from the Deak group are relevant (Gano et al., Cytokine; Doremus-Fitzwater et al., Frontiers in Behavioral Neuroscience).
    Minor edits:
    Abstract line 2 – affect not effect
    P. 7 – oligodendrocytes should be separate paragraph (also on p.10). Define OPC at first use
    On p.12 the sentence “Microglia exhibited an activated morphology, and levels of the pro-inflammatory cytokines IL-1β and TNF-α, and chemokine CCL2, were elevated in animals treated with ethanol in all three brain regions” should be changed to “Microglia exhibited an activated morphology, and levels of the pro-inflammatory cytokines IL-1β and TNF-α, and chemokine CCL2, were elevated in all three brain regions in animals treated with ethanol.”

    P.12. line 31 – what is the definition of “moderate ethanol exposure” and of “severe ethanol exposure”?

    p. 13. Line 14-18 One of the words “postnatal” in this sentence is redundant. Line 24 – what age(s) is included in “early postnatal rats”. Lines 22-31 – the information on micro-hemhorrages is not integrated.

    p.14 second sentence – does the apoptosis persist into adulthood?

    Reviewed by
    Cite this review
All peer review content displayed here is covered by a Creative Commons CC BY 4.0 license.