Chronic inflammation, cognitive impairment, and distal brain region alteration following intracerebral hemorrhage

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Delayed cognitive decline commonly occurs following intracerebral hemorrhage (ICH), but the mechanisms underlying this phenomenon remain obscure. We therefore investigated the potential mechanisms responsible for impaired cognitive function in a mouse collagenase model of ICH. Following recovery of motor and sensory deficits in the chronic phase of ICH, we noted significant cognitive impairment, which was assessed by the Morris water maze. This finding was accompanied by reduced dendrite spine density of ipsilateral hippocampal CA1 neurons. Reduced synaptic plasticity, manifested by impaired long-term potentiation in hippocampal neurons, was also evident in both ipsilateral and contralateral hemispheres, suggesting that ICH also induces functional alterations in distal brain regions remote from the site of injury. In addition, the accumulation of microglia, infiltration of peripheral immune cells, and generation of reactive oxygen species were observed in both contralateral and ipsilateral hemispheres up to 5 wk post-ICH. Furthermore, depletion of microglia using PLX3397, which inhibits colony stimulating factor 1 receptor, ameliorated this delayed cognitive impairment. Collectively, these results suggest that persistent and diffuse brain inflammation may contribute to cognitive impairment in the chronic stage of ICH recovery.-Shi, E., Shi, K., Qiu, S., Sheth, K. N., Lawton, M. T., Ducruet, A. F. Chronic inflammation, cognitive impairment, and distal brain region alteration following intracerebral hemorrhage.

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Aminopyridines (pharmacology); Animals; Brain (metabolism); Cerebral Hemorrhage (immunology, metabolism); Cognition (drug effects); Cognitive Dysfunction (immunology, metabolism); Disease Models, Animal; Fingolimod Hydrochloride (pharmacology); Flow Cytometry; Hippocampus (metabolism); Inflammation (immunology, metabolism); Male; Mice; Mice, Inbred C57BL; Microglia (metabolism); Neuroimaging; Neuronal Plasticity (drug effects); Pyrroles (pharmacology); Receptors, Granulocyte-Macrophage Colony-Stimulating Factor (antagonists & inhibitors, metabolism)

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FASEB journal : official publication of the Federation of American Societies for Experimental Biology







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