Mechanisms of action of acute and subacute sphenopalatine ganglion stimulation for ischemic stroke

Abstract

Background Sphenopalatine ganglion stimulation (SPG-Stim) for ischemic stroke, starting 8–24 h after onset and continuing through five days in a pooled analysis of two recent, randomized, sham-controlled trials, improved outcome of acute ischemic stroke patients with confirmed cortical involvement. As a neuromodulatory therapy, SPG-Stim differs substantially from existing pharmacologic (lytic and antiplatelets) and device (endovascular thrombectomy) acute ischemic stroke treatments. Aim Focused review of SPG anatomy, physiology, and neurovascular and neurobiologic mechanisms of action mediating benefit of SPG-Stim in acute ischemic stroke. Summary of review Located posterior to the maxillary sinus, the SPG is the main source of parasympathetic innervation to the anterior circulation. Preclinical and human studies delineate four distinct mechanisms of action by which the SPG-Stim may confer benefit in acute ischemic stroke: (1) collateral vasodilation and enhanced cerebral blood flow, mediated by release of neurotransmitters with vasodilatory effects, nitric oxide, and acetylcholine, (2) stimulation frequency- and intensity-dependent stabilization of the blood–brain barrier, reducing edema (3) direct acute neuroprotection from activation of the central cholinergic system with resulting anti-inflammatory, anti-apoptotic, and anti-excitatory effects; and (4) neuroplasticity enhancement from enhanced central cholinergic and adrenergic neuromodulation of cortical networks and nitrous oxide release stimulating neurogenesis. Conclusion The benefit of SPG-Stim in acute ischemic stroke is likely conferred not only by potent collateral augmentation, but also blood–barrier stabilization, direct neuroprotection, and neuroplasticity enhancement. Further studies clarifying the relative contribution of these mechanisms and the stimulation protocols that maximize each may help optimize SPG-Stim as a therapy for acute ischemic stroke.

Osteopathic Manipulation of the Sphenopalatine Ganglia Versus Sham Manipulation, in Obstructive Sleep Apnoea Syndrom: A Randomised Controlled Trial

“…The mechanism of action in these diseases is blockade of the trigeminovascular network of which the SPG is a component and, more precisely, blockade of the parasympathetic autonomic vasomotor system that is responsible, among other things, for nasal congestion [ 12 ]. In contrast, in stroke, SPG neuromodulation by implanted stimulation targets a stimulant effect on the parasympathetic nervous system [ 36 ] with a demonstrated benefit in terms of increased cerebral blood flow secondary to the release of vasodilator neurotransmitters (Nitric Oxide, acetylcholine), decreased cerebral oedema due to stabilisation of the blood-brain barrier, and potentially a neuroprotective effect [ 37 ]. In particular, it should be noted that high-frequency implanted SPG stimulation induces a reduction of postganglionic parasympathetic activity [ 13 ], while a parasympathetic stimulant effect is observed in response to low-frequency stimulation, with the consequent risk of cluster-like attacks [ 38 ].…”

The Utility of Domain-Specific End Points in Acute Stroke Trials

“…Some acute therapies target specific penumbral areas, eg, via brain stimulation. 42,43 Endovascular therapy can in some instances preferentially target elegant or eloquent cortex, 44 an approach that can be guided by weighting affected brain voxels according to the functional consequences of infarction. 45 For these approaches to acute stroke therapy, measuring the behavioral output of target neural system(s) using domain-specific end points, as compared to global end points, would likely improve detection of efficacy.…”

Biomarkers of Angiogenesis and Neuroplasticity as Promising Clinical Tools for Stroke Recovery Evaluation

“…The neuroplastic process is related to synaptogenesis, neurogenesis, and neuroprotection. In a stroke, neuroplasticity begins immediately after an ischemic event under the critical conditions of inflammation, edema, metabolic disturbances, apoptosis, and nerve fiber degeneration [38]. Neuroplasticity is a very complex process, which remains unclear and relies on the consolidation of existing synaptic pathways to create new connections.…”