Nimodipine Attenuation of Early Brain Dysfunctions Is Partially Related to its Inverting Acute Vasospasm in a Cisterna Magna Subarachnoid Hemorrhage (SAH) Model in Rats

Abstract

Subarachnoid hemorrhage (SAH)-induced brain injury is highly related to neurological deficits and mortality. Regional cerebral blood flow (rCBF) changes and vasoconstriction are two complications that occur soon after SAH experimentally. In this study we investigated the changes in rCBF and vertebro-basilar arterial diameter in a cisterna megna SAH model in Sprague-Dawley rats and intended to explore whether improving early rCBF reduction and cerebral vasospasm could contribute to alleviating blood-brain barrier (BBB) dysfunction. In rats for rCBF, vasospasm and BBB permeability assessments, nimodipine (NDP) or saline was administered intravenously 5 minutes after SAH. rCBF within the first 60 minutes after SAH was measured by laser Doppler flowmetry. BBB permeability indexed by Evans Blue extravasation was assessed 4 hours after SAH. Angiography for the caliber changes of the vertebro-basilar artery were conducted 30 minutes post SAH. Pronounced rCBF reduction and vasospasm were observed soon after SAH, followed by BBB permeability increment. NDP administration could improve rCBF and attenuate vasospasm, followed by the alleviation of BBB permeability. Our results demonstrate that early improvement of cerebral circulation by NDP may contribute to the reduction in brain injury indexed by BBB disruption.

Calcium and Potassium Channels in Experimental Subarachnoid Hemorrhage and Transient Global Ischemia

“…Intravenous administration of nimodipine five minutes after SAH improves circulation and attenuates vasospasm in rats [54]. Nicardipine (dihydropyridine) pellets positioned next to the basal arteries have been shown to reduce the occurrence of angiographic vasospasm in a dose-dependent manner in patients suffering from SAH [55, 56].…”

Impact of Early Versus Late Intravenous Followed by Oral Nimodipine Treatment on the Occurrence of Delayed Cerebral Ischemia Among Patients With Aneurysm Subarachnoid Hemorrhage

“…2,19 Therefore, early improvement of hypoxia by increasing cerebral blood flow or reducing vasospasm with nimodipine may contribute to decreased brain injury and safeguard neurons. 5,6 As mentioned earlier, IV nimodipine delivered higher concentrations of nimodipine in plasma, neuron, and cerebrospinal fluid than oral. Therefore, early treatment with IV nimodipine might have the potential to reduce severity of vasospasm after aSAH and decrease DCI occurrence better than oral nimodipine treatment.…”

“…5 Nimodipine decreased rat brain ischemia by improving cerebral blood flow, then reducing vasospasm to mitigate blood-brain barrier injury. 6 Moreover, the British Aneurysm Nimodipine Trial compared clinical outcomes following aSAH between oral nimodipine treatment within 96 hours and placebo. 7 This demonstrated that nimodipine produced significantly better outcomes, with 34% lowering of cerebral infarction and 40% poor outcome diminution.…”

Multimodal MRI characterization of experimental subarachnoid hemorrhage

“…1 Vasospasm was detected immediately after SAH (30 mins) but not thereafter, indicating that vasospasm is transient in this mild SAH model. Previous studies using ex vivo arteries 41–43 and in vivo angiography 44,45 in relatively more severe SAH models have detected vasospasm. Specifically, an MRI study of a SAH model by puncturing the vessel found narrowing of vessels but vasoconstriction only reached significance in the right proximal ICA in the acute phase and returned to normal on day 9.…”