Calcitonin gene-related peptide reduces brain injury in a rat model of focal cerebral ischemia.
OBJECTIVE
Calcitonin gene-related peptide is an endogenous vasodilating neuropeptide with a dense concentration in the trigeminocerebrovascular system. It is hypothesized that depletion of this peptide contributes to delayed cerebral ischemia after subarachnoid hemorrhage and that an exogenous supply of calcitonin gene-related peptide will augment ischemic cerebral blood flow and reduce neuronal injury.


METHODS
In this study we have investigated the effect of an intravenous infusion of calcitonin gene-related peptide (100 ng/kg per minute), started 1 hour before and continued throughout 4 hours of focal cerebral ischemia, on cerebral blood flow and the volume of brain injury in a rat model of middle cerebral artery occlusion.


RESULTS
Calcitonin gene-related peptide produces a significant improvement in ischemic cerebral blood flow (32 +/- 2 compared with 13 +/- 2 mL/100 g per minute in the controls; t = 6.92, P < .0001) with a concomitant reduction in the volume of ischemic brain injury (102 +/- 22 compared with 234 +/- 19 mm3; t = 4.47, P < .001).


CONCLUSIONS
These findings lend support for the potential use of this peptide in the prophylactic treatment of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.
Holland
J P
JP
Division of Clinical Neuroscience, St George's Hospital Medical School, Atkinson Morley's Hospital, Wimbledon, London, UK.
Sydserff
S G
SG
Taylor
W A
WA
Bell
B A
BA
D000818:Animals; D001479:Basal Ganglia / Q000473:pathology; D001925:Brain Damage, Chronic / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D007262:Infusions, Intravenous; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009474:Neurons / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology; D014664:Vasodilation / Q000502:physiology
D015740:Calcitonin Gene-Related Peptide