Effects of isradipine, an L-type calcium channel blocker on permanent and transient focal cerebral ischemia in spontaneously hypertensive rats.
Permanent or transient focal cerebral ischemia was induced in spontaneously hypertensive rats (SHR) using the intraluminal filament method. Successful occlusion of the middle cerebral artery (MCA) was achieved using 4/O filaments (terminal diameter 0.20-0.25 mm) coated with poly-L-lysine. The L-type calcium channel blocker isradipine (2.5 mg/kg) administered subcutaneously 30 min following permanent MCA occlusion significantly reduced the volume of ischemic brain damage in the cerebral hemisphere (25%; P = 0.0001), cerebral cortex (18%; P = 0.0034), and caudate nucleus (33%; P = 0.0002) when assessed at 24 h post-MCA occlusion. Isradipine did not affect the functional deficit (measured using a subjective neurological scoring system) induced by MCA occlusion. In SHR undergoing transient (2 h) MCA occlusion isradipine administered 30 min post-MCA occlusion produced a significant reduction (47%; P = 0.001) in hemispheric infarct volume, whereas isradipine administered at the onset of reperfusion did not confer any significant neuroprotection. No change in functional deficit was seen with isradipine with either dosing paradigm at 24 h post-MCA occlusion. These results demonstrate that the intraluminal filament method of MCA occlusion can be used in the SHR strain and also substantiates the neuroprotective efficacy of isradipine in SHR models of permanent and transient focal cerebral ischemia.
Campbell
C A
CA
SmithKline Beecham Pharmaceuticals, Harlow, Essex, United Kingdom.
Mackay
K B
KB
Patel
S
S
King
P D
PD
Stretton
J L
JL
Hadingham
S J
SJ
Hamilton
T C
TC
D000818:Animals; D001522:Behavior, Animal; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015220:Calcium Channels / Q000187:drug effects*; D020746:Calcium Channels, L-Type; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017275:Isradipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D017275:Isradipine