Long-Term Hyperexcitability in the Hippocampus after Experimental Head Trauma.
Abstract number :
I.03
Submission category :
Year :
2001
Submission ID :
251
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
V. Santhakumar, Anatomy & Neurobiology, University of California, Irvine, Irvine, CA; A.D.H. Ratzliff, Anatomy & Neurobiology, University of California, Irvine, Irvine, CA; I. Soltesz, Anatomy & Neurobiology, University of California, Irvine, Irvine, CA
RATIONALE: Head injury is an etiological factor in the development of temporal lobe epilepsy. However, whether a single episode of concussive head trauma causes a persistent increase in neuronal excitability in the limbic system has not been unequivocally determined.
METHODS: This study used the rodent fluid percussion injury (FPI) model, in combination with electrophysiological and histochemical techniques, to investigate the early (one week) and long-term (one month or longer) changes in the hippocampus after head trauma.
RESULTS: Low frequency single-shock stimulation of the perforant path revealed an early granule cell hyperexcitability in head-injured animals that returned to control levels by one month. However, there was a persistent decrease in threshold to induction of seizure-like electrical activity in response to high-frequency tetanic stimulation in the hippocampus after head injury. Timm staining revealed both early and long-term mossy fiber sprouting at low to moderate levels in the dentate gyrus of animals that experienced FPI. There was a long-lasting increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) in dentate granule cells after FPI, and ionotropic glutamate receptor antagonists selectively decreased the sIPSC frequency in the head-injured animals.
CONCLUSIONS: These results demonstrate that a single episode of experimental closed head trauma induces long-lasting alterations in the hippocampus. These persistent structural and functional alterations in inhibitory and excitatory circuits are likely to influence the development of hyperexcitable foci in post-traumatic limbic circuits.
Support: NIH (NS35916 to I.S.)