Aberrant hippocampal mossy fiber sprouting correlates with greater NMDAR2 receptor staining

Gary W. Mathern, Joao P. Leite, Thomas L. Babb, James K. Pretorius, Paula A. Kuhlman, Delia Mendoza, Itzhak Fried, Americo C. Sakamoto, Joao A. Assirati, P. David Adelson, Warwick J. Peacock

Research output: Contribution to journalArticlepeer-review


This study determined in temporal lobe epilepsy patients and rats injected with intrahippocampal kainate (KA) whether fascia dentata molecular layer mossy fiber sprouting was associated with increases in NMDAR2 immunoreactivity (IR). Patients with hippocampal sclerosis (n = 11) were compared with those with temporal mass lesions (n = 7) and material obtained at autopsies (n = 4); and unilateral KA-injected rat hippocampi (n = 7) were compared with the contralateral saline-injected side and non-lesioned animals (n=7; control). Hippocampi were studied for neo-Timm's stained mossy fiber sprouting and NMDAR2 IR. The staining was quantified as gray values (GV) using computer image analysis. Hippocampal sclerosis patients and KA-injected rats showed the greatest inner molecular layer (IML) mossy fiber sprouting and NMDAR2 staining. Compared with autopsies and patients with mass lesions, hippocampal sclerosis patients had greater IML neo-Timm's (p=0.0018) and NMDAR2 staining (p=0.0063). Similarly, compared with controls and saline- injected rats, KA-injected hippocampi showed greater IML mossy fiber sprouting and NMDAR2 IR (p=0.0001). Furthermore, IML mossy fiber sprouting positively correlated with greater IML NMDAR2 staining in both human and experimental rat groups (p<0.0099). These results support the hypothesis that in severely damaged hippocampi abnormal mossy fiber sprouting and concordant increases in IML NMDAR2 receptor staining may contribute or partially explain granule cell hyperexcitability and the pathophysiology of hippocampal epilepsy.

Original languageEnglish
Pages (from-to)1029-1035
Number of pages7
Issue number5
StatePublished - 1996
Externally publishedYes


  • Complex partial seizures
  • Epilepsy
  • Excitation
  • NIH image
  • Reactive synaptogenesis


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