Translational Brain Research Laboratory, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Department of Neurosurgery, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.
Neurosurgery. 2021 May 13;88(6):E529-E536. doi: 10.1093/neuros/nyab053.
The trigeminal nerve directly innervates key vascular structures both centrally and peripherally. Centrally, it is known to innervate the brainstem and cavernous sinus, whereas peripherally the trigemino-cerebrovascular network innervates the majority of the cerebral vasculature. Upon stimulation, it permits direct modulation of cerebral blood flow (CBF), making the trigeminal nerve a promising target for the management of cerebral vasospasm. However, trigeminally mediated cerebral vasodilation has not been applied to the treatment of vasospasm.
To determine the effect of percutaneous electrical stimulation of the infraorbital branch of the trigeminal nerve (pTNS) on the cerebral vasculature.
In order to determine the stimulus-response function of pTNS on cerebral vasodilation, CBF, arterial blood pressure, cerebrovascular resistance, intracranial pressure, cerebral perfusion pressure, cerebrospinal fluid calcitonin gene-related peptide (CGRP) concentrations, and the diameter of cerebral vessels were measured in healthy and subarachnoid hemorrhage (SAH) rats.
The present study demonstrates, for the first time, that pTNS increases brain CGRP concentrations in a dose-dependent manner, thereby producing controllable cerebral vasodilation. This vasodilatory response appears to be independent of the pressor response induced by pTNS, as it is maintained even after transection of the spinal cord at the C5-C6 level and shown to be confined to the infraorbital nerve by administration of lidocaine or destroying it. Furthermore, such pTNS-induced vasodilatory response of cerebral vessels is retained after SAH-induced vasospasm.
Our study demonstrates that pTNS is a promising vasodilator and increases CBF, cerebral perfusion, and CGRP concentration both in normal and vasoconstrictive conditions.
三叉神经直接支配中枢和外周的关键血管结构。中枢方面，已知其支配脑干和海绵窦，而外周三叉神经-脑血管网络支配大脑血管的大部分。刺激三叉神经会直接调节脑血流量（CBF），使三叉神经成为治疗脑血管痉挛的有前途的靶点。然而，三叉神经介导的脑血管扩张尚未应用于治疗血管痉挛。
确定三叉神经眶下支经皮电刺激（pTNS）对脑血管的影响。
为了确定 pTNS 对脑血管扩张的刺激反应功能，在健康和蛛网膜下腔出血（SAH）大鼠中测量了 CBF、动脉血压、脑血管阻力、颅内压、脑灌注压、脑脊液降钙素基因相关肽（CGRP）浓度和脑血管直径。
本研究首次证明，pTNS 以剂量依赖的方式增加大脑 CGRP 浓度，从而产生可控制的脑血管扩张。这种血管扩张反应似乎独立于 pTNS 引起的升压反应，因为即使在 C5-C6 水平切断脊髓后，它仍然存在，并且通过给予利多卡因或破坏它来证明它仅限于眶下神经。此外，在 SAH 引起的血管痉挛后，pTNS 诱导的脑血管扩张反应仍然保留。
我们的研究表明，pTNS 是一种有前途的血管扩张剂，可增加正常和血管收缩条件下的 CBF、脑灌注和 CGRP 浓度。
