Microglial activation occurs in the absence of anxiety-like behavior following microembolic stroke in female, but not male, rats

Journal of Neuroinflammation

Gretchen N Neigh¹  Jabari Bailey¹  Mandakh Bekhbat¹  Renuka Reddy¹  Christina L Nemeth¹ 

[1] Department of Physiology, Emory University, Atlanta, GA, USA

关键词: Microglia;    Behavior;    Animal model;    Vascular ischemia;    Sex differences;   

Others  :  1150291
DOI  :  10.1186/s12974-014-0174-7

 received in 2014-04-11, accepted in 2014-09-28,  发布年份 2014

【 摘 要 】

Background

The incidence of depression and anxiety disorders is twice as high in women than men; however, females exhibit less neuronal damage following an equivalent ischemic event. Microembolic stroke increases anxiety- and depressive-like behaviors in male rats but the behavioral repercussions in females are unknown.

Findings

Given the relative neuronal protection from stroke in ovary-intact females, female rats exposed to microembolic stroke may be behaviorally protected as compared to males. The data presented demonstrate that anxiety-like behavior is increased in males despite a comparable increase in microglial activation following microembolic stroke in both males and females.

Conclusions

These data suggest that males may be more behaviorally susceptible to the effects of microembolic stroke and further illustrate a dissociation between neuroinflammation and behavior in females.

【 授权许可】

   
2014 Nemeth et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie KL, Howard VJ, Lichtman JH, Lisabeth LD, Pina IL, Reeves MJ, Rexrode KM, Saposnik G, Singh V, Towfighi A, Vaccarino V, Walters MR: Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014, 45:1545-1588.
• [2]Manwani B, McCullough LD: Sexual dimorphism in ischemic stroke: lessons from the laboratory. Womens Health 2011, 7:319-339.
• [3]Wagner AK, Willard LA, Kline AE, Wenger MK, Bolinger BD, Ren D, Zafonte RD, Dixon CE: Evaluation of estrous cycle stage and gender on behavioral outcome after experimental traumatic brain injury. Brain Res 2004, 998:113-121.
• [4]Xiong Y, Mahmood A, Lu D, Qu C, Goussev A, Schallert T, Chopp M: Role of gender in outcome after traumatic brain injury and therapeutic effect of erythropoietin in mice. Brain Res 2007, 1185:301-312.
• [5]Wendell C, Hosey M, Lefkowitz D, Katzel L, Siegel E, Rosenberger W, Waldstein S: Depressive symptoms are associated with subclinical cerebrovascular disease among healthy older women, not men. Am J Geriatr Psychiatry 2010, 18:940-947.
• [6]Nemeth CL, Shurte MS, McTigue DM, Nemeroff CB, Neigh GN: Microembolism infarcts lead to delayed changes in affective-like behaviors followed by spatial memory impairment. Behav Brain Res 2012, 234:259-266.
• [7]Neigh GN, Karelina K, Glasper ER, Bowers SLK, Zhang N, Popovich PG, DeVries AC: Anxiety after cardiac arrest/cardiopulmonary resuscitation: exacerbated by stress and prevented by minocycline. Stroke 2009, 40:3601-3607.
• [8]Wohleb ES, Powell ND, Godbout JP, Sheridan JF: Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior. J Neurosci 2013, 33:13820-13833.
• [9]Wohleb ES, Patterson JM, Sharma V, Quan N, Godbout JP, Sheridan JF: Knockdown of interleukin-1 receptor type-1 on endothelial cells attenuated stress-induced neuroinflammation and prevented anxiety-like behavior. J Neurosci 2014, 34:2583-2591.
• [10]Li J, Siegel M, Yuan M, Zeng Z, Finnucan L, Persky R, Hurn PD, McCullough LD: Estrogen enhances neurogenesis and behavioral recovery after stroke. J Cereb Blood Flow Metab 2011, 31:413-425.
• [11]Alkayed NJ, Harukuni I, Kimes AS, London ED, Traystman RJ, Hurn PD, Grady PA: Gender-linked brain injury in experimental stroke - editorial comment. Stroke 1998, 29:159-166.
• [12]Hinwood M, Tynan RJ, Charnley JL, Beynon SB, Day TA, Walker FR: Chronic stress induced remodeling of the prefrontal cortex: structural re-organization of microglia and the inhibitory effect of minocycline. Cereb Cortex 2013, 23:1784-1797.
• [13]Moisse K, Welch I, Hill T, Volkening K, Strong MJ: Transient middle cerebral artery occlusion induces microglial priming in the lumbar spinal cord: a novel model of neuroinflammation. J Neuroinflamm 2008, 5:29. BioMed Central Full Text
• [14]Perry VH, Holmes C: Microglial priming in neurodegenerative disease. Nat Rev Neurol 2014, 10:217-224.
• [15]Pyter LM, Kelly SD, Harrell CS, Neigh GN: Sex differences in the effects of adolescent stress on adult brain inflammatory markers in rats. Brain Behav Immune 2013, 30:88-94.
• [16]Zhang L, Nair A, Krady K, Corpe C, Bonneau R, Simpson I, Vannucci S: Estrogen stimulates microglia and brain recovery from hypoxia-ischemia in normoglycemic but not diabetic female mice. J Clin Invest 2004, 113:85-95.
• [17]Smith AL, Alexander M, Rosenkrantz TS, Sadek ML, Fitch RH: Sex differences in behavioral outcome following neonatal hypoxia ischemia: insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic brain injury. Exp Neurol 2014, 254:54-67.