Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5

Abstract

Depression of electrocorticogram propagating over the cortex surface results in cortical spreading depression (CSD), which is probably related to the pathophysiology of stroke, epilepsy, and migraine. However, preconditioning with CSD produces neuroprotection to subsequent ischemic episodes. Such effects require the expression or activation of several genes, including neuroprotective ones. Recently, it has been demonstrated that the expression of the uncoupling proteins (UCPs) 2 and 5 is amplified during brain ischemia and their expression exerts a long-term effect upon neuron protection. To evaluate the neuroprotective consequence of CSD, the expression of UCP-5 in the brain cortex was measured following CSD induction. CSD was evoked in four samples of rats, which were sacrificed after 2 hours, 4 hours, 6 hours, and 24 hours. Western blot analyses were carried out to measure UCP-5 concentrations in the prefrontal cortices of both hemispheres, and immunohistochemistry was performed to determine the localization of UCP-5 in the brain cortex. The results showed a significant elevation in UCP-5 expression at 24 hours in all cortical strata. Moreover, UCP-5 was triggered by CSD, indicating that UCP-5 production can have a neuroprotective effect.

Keywords: cortical spreading depression; neuroprotective effect; uncoupling protein-5.

Figure 1

CSD increases UCP-5 expression at 24 hours. Notes: (A) Representative Western blot analysis of UCP-5. Coomassie Blue stain of total protein in loading control. Proteins were extracted from the cortex of both hemispheres at 2 hours, 4 hours, 6 hours, or 24 hours after CSD. (B) Densitometric analysis of UCP-5 in the CSD-treated cortex expressed as a fold rise versus control (untreated cortex). Data are mean ± SEM (P<0.05). *P<0.05 compared to the control. Abbreviations: CSD, cortical spreading depression; Ctr, control; SEM, standard error of the mean; h, hours.

Figure 2

Pseudocolor image of immunohistochemical demonstration of UCP5 expression in the rat cerebral cortex at 24 hours after NaCl application (A) control and (B) after CSD induction with KCl. Notes: The signal was higher in the treated cortex compared to the control. Pseudocolor scale: green, high signal; blue, low signal. Magnification ×10 on the right, which are magnified areas represented by the square in the left figures, with ×40 on the left. Bar =0.1 mm. Abbreviation: CSD, cortical spreading depression.