1223. Subarachnoid Hemorrhage (SAH) -Induced Hippocampal Morphological And Physiological Disorders.
Authors: Gavin W. Britz, MD, FAANS; Evgueniy Bovshik; Angelique Regnier-Golanov; Eugene Golanov, MD, PhD (Houston, TX)
Introduction: Overwhelming majority of SAH survivors experience various long-term memory and cognitive abnormalities. Atrophy of the temporomesial area observed in SAH survivors is suggestive of hippocampal abnormalities following SAH. We hypothesize that SAH induces long-term complement-dependent pathological changes in hippocampal formation. Methods: Upon histological examination, we did not observe blood in the ventricles or presence of iron in the hippocampus. Number of cells in CA1 area was comparable in Sham and SAH animals and no fluoro-jade C or activated caspase 3-positive staining was observed in CA1 or DG. Immunoreactivity of GFAP (astrocyte marker) and Iba1 (microglial marker) increased respectively by 2- (p=0.013) and 1.5-fold (p=0.038) in CA1 and DG areas compared to Sham suggesting activation of astro- and microglial cells, while the intensity of MAP2 (dendrite marker) staining decreased by 1.6 fold (p=0.031). Hippocampal neuroinflammation was accompanied by loss of dendritic spines of the DG and CA1 neurons (p<0.001) and suppression of LTP in DG and CA1 (p<0.05). Intracerebroventricular administration of compstatin, an inhibitor of C3 which is a central complement component, reversed suppression of LTP and loss of dendritic spines. Conclusion: Our data demonstrate development of hippocampal neuroinflammation at 4 days following SAH. Reversal of hippocampal functional and morphological abnormalities by blocking of C3 suggests involvement of the complement system in SAH-induced hippocampal disturbances.