title: Mossy fiber reorganization and its possible physiological consequences in the dentate gyrus of epileptic humans.
abstract: It is unlikely that MF reorganization is the cause of epilepsy, but it may affect the progression of the disease, i.e., the frequency or severity of seizures. We propose that early events, yet undiscovered, lead to an increased likelihood of excitability. This hyperexcitability, which initially may not be manifested in overt seizures, may erode vulnerable hilar neurons that serve an important inhibitory function, as illustrated in Fig. 6-15. As inhibition is lost, hyperexcitability reaches the level of clinically manifested seizures that are severe enough to lead to substantial loss of hilar neurons. When the loss of these cells is sufficiently high, MF reorganization occurs, first to neighboring hilar neurons and later to dendrites of granule cells (Fig. 6-15). Thus, the functional consequence of MF reorganization may provide a compensatory form of inhibition, as well as a circuit for feedback excitation. Although definitive evidence indicating that MF reorganization contributes to the acceleration or progression of epilepsy is missing, the findings to date are consistent with this hypothesis. In the event that reorganization contributes to the epileptic condition, treatments that reduce indicators of neuropathology may lead to a reduction of seizure frequency and severity. Evidence suggests that reorganization in the dentate gyrus may follow the pathways of neuronal processes of hilar neurons that have died. Thus, further study of the events that guide MF reorganization may hold important clues for developing methods for targeting regenerating axons following central nervous system injury.
authors.affiliation: Department of Neurology, Graduate Hospital, Philadelphia, Pennsylvania, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Masukawa
authors.forename: W M
authors.initials: WM
authors.lastname: O'Connor
authors.forename: L J
authors.initials: LJ
authors.lastname: Burdette
authors.forename: P
authors.initials: P
authors.lastname: McGonigle
authors.forename: M R
authors.initials: MR
authors.lastname: Sperling
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connor
authors.forename: K
authors.initials: K
authors.lastname: Uruno
mesh_terms: D018891:Dentate Gyrus / Q000473:pathology* / Q000503:physiopathology*; D004827:Epilepsy / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D009410:Nerve Degeneration / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology*