Mechanisms of the anti-ischemic effect of vagus nerve stimulation in the gerbil hippocampus

Abstract

The neuroprotective mechanisms of cervical vagus nerve stimulation (VNS) in transient ischemia were investigated. Left VNS (0.4 mA, 40 Hz) was performed during 5 min ischemia in gerbils. About 50% of the hippocampal neurons were rescued from ischemic insult by VNS, and this effect was prevented by transection of the vagus nerve centrally to the site of cervical stimulation. VNS significantly attenuated both ischemia-induced glutamate release and transient increase of hippocampal blood flow during reperfusion. Hyperemia as well as excessive glutamate release after ischemia is regarded as an important factor in ischemic brain damage as it leads to generate considerable reactive oxygen species. Thus, VNS might protect neurons from ischemia-induced glutamate excitotoxicity and reperfusion injury via the afferent path-way of the vagus.

The Parasympathetic Nervous System in the Quest for Stroke Therapeutics

“…Electrical VNS has been shown to attenuate cerebral ischemic injury (Ay et al, 2009;Miyamoto et al, 2003). In a transient model of focal cerebral ischemia (2 hours of ischemia followed by reperfusion) in rats, Ay et al (2009) found that VNS significantly decreased infarct size and neurologic deficit at 24 hours after ischemia/reperfusion.…”

“…In a transient model of focal cerebral ischemia (2 hours of ischemia followed by reperfusion) in rats, Ay et al (2009) found that VNS significantly decreased infarct size and neurologic deficit at 24 hours after ischemia/reperfusion. In a mechanistic approach, Miyamoto et al (2003) found that VNS significantly decreased extracellular glutamate levels between 15 and 20 minutes after 5 minutes of transient global ischemia model in Mongolian gerbils. Excessive glutamate release has a role in excitotoxicity during cerebral ischemia through the activation of N-methyl-D-aspartate receptor (Bosel et al, 2005;Choi, 1985).…”

“…The effect of VNS on ischemic stroke was investigated in two different laboratories using rodent transient cerebral ischemia models, with some form of physiological monitoring during experiments (Ay et al, 2009;Miyamoto et al, 2003). In one study (Ay et al, 2009), animal allocation was randomized and assessment of outcome blinded, in contrast to the other study (Miyamoto et al, 2003).…”

“…In one study (Ay et al, 2009), animal allocation was randomized and assessment of outcome blinded, in contrast to the other study (Miyamoto et al, 2003). Overall, the effect of VNS on ischemic stroke needs to be more rigorously assessed using both permanent and transient cerebral ischemia models in both rodents and gyrencephalic species such as primates, with randomization and blinding of outcome assessment.…”

“…However, PNS activation has not yet been successfully developed as a therapy for stroke. Optimistically, various forms of PNS activation, namely VNS (Ay et al, 2009;Miyamoto et al, 2003), sphenopalatine ganglion (SPG) stimulation (Yarnitsky et al, 2006), cholinesterase inhibitors (Akasofu et al, 2003), and a7 nicotinic acetylcholine receptor (nAChRa7) agonists (Parada et al, 2010) have shown neuroprotection in both preclinical models of cerebral ischemia and in vitro neuronal hypoxia. The mechanisms involved in these neuroprotective effects remain unclear.…”