ABERRANT HIPPOCAMPAL MOSSY FIBER SPROUTING CORRELATES WITH GREATER NMDAR2 RECEPTOR STAINING

THIS study determined in temporal lobe epilepsy patients and rats inje cted with intrahippocampal kainate (KA) whether fascia dentata molecul ar layer messy fiber sprouting was associated with increases in NMDAR2 immunoreactivity (IR). Patients with hippocampal sclerosis (n = 11) w ere compared with those with temporal mass lesions (n = 7) and materia l obtained at autopsies (n = 4); and unilateral KA-injected rat hippoc ampi (n = 7) were compared with the contralateral saline-injected side and non-lesioned animals (n = 7; control). Hippocampi were studied fo r neo-Timm's stained messy fiber sprouting and NMDAR2 IR. The staining was quantified as gray values (GV) using computer image analysis. Hip pocampal sclerosis patients and KA-injected rats showed the greatest i nner molecular layer (IML) messy fiber sprouting and NMDAR2 staining. Compared with autopsies and patients with mass lesions, hippocampal sc lerosis patients had greater IML neo-Timm's (p = 0.0018) and NMDAR2 st aining (p = 0.0063). Similarly, compared with controls and saline-inje cted rats, KA-injected hippocampi showed greater IML messy fiber sprou ting and NMDAR2 IR (p = 0.0001). Furthermore, IML messy fiber sproutin g positively correlated with greater IML NMDAR2 staining in both human and experimental rat groups (p < 0.0099). These results support the h ypothesis that in severely damaged hippocampi abnormal messy fiber spr outing and concordant increases in IML NMDAR2 receptor staining may co ntribute or partially explain granule cell hyperexcitability and the p athophysiology of hippocampal epilepsy.