A new class of heat shock protein co-inducer dihydropyridine derivatives devoid of
calcium channel antagonist and vasodilator effects have been recently developed with
the purpose to target neurodegeneration selectively. Here we set out to evaluate the
action of one of these novel compounds LA1011 on neurovascular coupling in the ischemic
rat cerebral cortex. As a reference, we applied nimodipine, a well-known calcium channel
antagonist, vasodilator dihydropyridine compound.Rats (n=62) were treated with LA1011
or nimodipine, either by chronic, systemic (LA1011, 1 mg/kg b.w.), or acute, local
administration (LA1011 and nimodipine, 100 μM). In the latter treatment group, global
forebrain ischemia was induced in half of the animals by bilateral common carotid
artery occlusion under isoflurane anesthesia. Functional hyperemia in the somatosensory
cortex was created by mechanical stimulation of the contralateral whisker pad under
alpha-chloralose anesthesia. Spreading depolarization (SD) events were elicited subsequently
by 1 M KCl. Local field potential and cerebral blood flow (CBF) in the parietal somatosensory
cortex were monitored by electrophysiology and laser Doppler flowmetry.LA1011 did
not alter CBF, but intensified SD, presumably indicating the co-induction of heat
shock proteins, and, perhaps an anti-inflammatory effect. Nimodipine attenuated evoked
potentials and SD. In addition to the elevation of baseline CBF, nimodipine augmented
hyperemia in response to both somatosensory stimulation and SD, particularly under
ischemia. In conclusion, in contrast with CBF improvement achieved by nimodipine,
LA1011 seems not to have discernible cerebrovascular effects, but may upregulate stress
response.