Seizures are common after severe
cerebral ischemia. To examine the mechanisms underlying these
seizures, we determined the impact of prior forebrain
ischemia on the seizure thresholds of four
convulsants with differing modes of action:
lidocaine,
pentylenetetrazol (PTZ),
N-methyl-D-aspartate (
NMDA), and
picrotoxin. Anesthetized Sprague-Dawley rats were chronically instrumented with screw
electrodes and
vascular catheters, and then subjected to 10 min of forebrain
ischemia, produced by carotid occlusion and
hypotension (mean arterial pressure to 30 mmHg). Animals were then awakened. 6, 24 or 48 h later, groups of awake animals received
intravenous infusions of the four drugs. The total dose of
drug infused prior to either electrical
seizures (
lidocaine, PTZ, and
picrotoxin) or
tonic-clonic convulsions (all drugs) were noted. For each
drug, a group of
Sham animals (no
ischemia) served as controls. There were markedly different patterns of changes in the
convulsant thresholds for the drugs. For example, at 6 h post-
ischemia, rats treated with
lidocaine died before convulsing, while the threshold for PTZ increased by 86%. There was no change in the
picrotoxin threshold at 6 h, but the dose of
NMDA needed to induce tonic-clonic seizure activity was reduced by 70%. By 48 h,
lidocaine and PTZ thresholds had returned to values similar to those in Shams, but the
NMDA threshold had now increased to a value 62% greater than
Sham. Ten minutes of
cerebral ischemia is followed by a complex and changing pattern of susceptibility to chemical
convulsants. Finding suggests that early post-ischemic
seizures may be related to increased
NMDA receptor sensitivity.