Neurogenic neuroprotection: clinical perspectives

Abstract

Neurogenic neuroprotection is a promising approach for treating patients with ischemic brain lesions. In rats, stimulation of the deep brain nuclei has been shown to reduce the volume of focal infarction. In this context, protection of neural tissue can be a rapid intervention that has a relatively long-lasting effect, making fastigial nucleus stimulation (FNS) a potentially valuable method for clinical application. Although the mechanisms of neuroprotection induced by FNS remain partially unclear, important data have been presented in the last two decades. A 1-h electrical FNS reduced, by 59%, infarctions triggered by permanent occlusion of the middle cerebral artery in Fisher rats. The acute effect of electrical FNS is likely mediated by a prolonged opening of potassium channels, and the sustained effect appears to be linked to inhibition of the apoptotic cascade. A better understanding of the neuronal circuitry underlying neurogenic neuroprotection may contribute to improving neurological outcomes in ischemic brain insults.

Figure 1

Characteristic burst-wave complexes recorded in parietal cortex of anesthetized rat. Upper row: (A) individual and (B) averaged (n = 25 sweeps) bursts recorded at slow sweep speeds followed by a single wave of vasodilation. Note that after averaging, the afterpotential of individual bursts disappears while only the initial potential remains. Reproduced with permission (Golanov and Reis, 1996a).

Figure 2

Neurogenic neuroprotection A 1-h electrical FNS (1 s on, 1 s off; 0.5 ms pulse durations, 75–150 mA) reduced infarctions triggered by permanent occlusion of the middle cerebral artery by 48–55% in Sprague-Dawley rats and by 59% in Fisher rats. The salvaging effect of FNS was long-lasting and reduced the volume of infarctions 72 h or 10 days later by 58 and 26%, respectively (Glickstein et al., 2001). As the effect appears to be global in the brain and given that the FN possesses relatively short projections, other relays must be involved in this network.