Jose Gutierrez, MD, MPH

Dreier et al. carried on an interesting experiment on rats to evaluate whether the commitment point of neurons distressed by spreading depression varies depending on the perfusion levels. Rats were assigned to three experimental groups: 1) A group where a K+-rich solution was applied to the brain surface through a small subdural window to induce a series of spreading depressions (SD), 2) A group where ischemia was forced by adding purified hemoglobin (nitric oxide scavenger) to the same K+ solution, and 3) A group where hyperemia was sought by adding nimodipine (a vasodilator) to the same K+/Hb+ solution used in group 2. The depolarizing potentials were measured with superficial and deep cortical electrodes and they lasted a little bit longer than an hour in each case. After the experiment was finished, the rats were sacrificed and the brain tissue was observed under the microscope to evaluate the degrees of inflammation, apoptosis, necrosis and asctrocytic activity in the three groups.

The investigators found that, as initially suspected, the greatest degree of necrosis involved all cortical layers and occurred in the groups where SD was accompanied by forced ischemia. Although the others 2 groups also suffered necrosis, this was limited to the superficial cortical layers. Greater degrees of inflammation were observed in the ischemic groups as well compared to the group where hyperemia was forced by adding nimodipine. The areas where necrosis was found recorded negative electric potential, suggesting that negative potentials might be markers of irreversible damage.   

The results of this animal experiment shed light on important aspects of the physiopathology of neuronal dysfunction in the setting of ischemia and electrochemical membrane failure. While not all effects observed in animals occur in a similar fashion in humans, this study opens potential research opportunities of broad clinical impact. Hyperemia for subarachnoid hemorrhage and permissive hypertension for acute stroke are examples of strategies currently in use where the concept of increased perfusion is applied to ischemic conditions. Understanding the mechanisms that can influence the commitment point at which neurons suffer irreversible damage is key in formulating successful neuroprotective strategies.