Abstract: Purpose: The most common pathology in temporal lobe epilepsy
(TLE) is hippocampal
sclerosis. It is controversial whether status epilepticus (SE) or prolonged
seizures plus secondary
cerebral injuries are pathogenic mechanisms of hippocampal sclerosis. This
study addressed this
question in rat models of TLE. Methods: Hippocampal neuron densities and
supragranular mossy
fiber sprouting were determined in adult rats subjected to systemic kainate-induced
SE (KA-only)
and KA-induced SE followed 75 minutes later by theophylline (KA/Theo) or
trimethobenzamide
(KA/Tri). These drugs probably decrease seizure-induced cerebral hyperemia
or hypertension.
Results: Compared with controls and KA-only rats, KA/Tri and KA/Theo rats
showed
decreased CA3b and CA1 neuron densities (i.e., greater Sommer's sector
injury). In addition,
KA/Tri rats showed that increased trimethobenzamide dosages were associated
with decreased
hilar, CA3c, CA3b, CA1, and subiculum neuron densities. There were no significant
differences
in supragranular mossy fiber sprouting between KA-only, KA/Tri, and KA/Theo
rats.
Conclusions: Pharmacologic manipulations during KA-induced SE are associated
with differences
in hippocampal pathology, especially in Sommer's sector, and the final
pattern of damage and
axon sprouting shows histopathologic similarities to that in patients with
hippocampal sclerosis.
Our findings support the hypothesis that secondary physiologic insults
during SE that are likely to
decrease seizure-induced cerebral hyperemia and hypertension may generate
greater
hippocampal neuronal injury compared with SE alone, and this may be a pathogenic
mechanism
of human hippocampal sclerosis in patients with TLE.