BACKGROUND AND PURPOSE: Using a rodent model of ischemia (permanent middle cerebral artery occlusion), our laboratory previously demonstrated that 4.27 minutes of patterned single-whisker stimulation delivered over 120 minutes can fully protect from impending damage when initiated within 2 hours of permanent middle cerebral artery occlusion ("early"). When initiated 3 hours postpermanent middle cerebral artery occlusion ("late"), stimulation resulted in irreversible damage. Here we investigate the effect of altering pattern, distribution, or amount of stimulation in this model. METHODS: We assessed the cortex using functional imaging and histological analysis with altered stimulation treatment protocols. In 2 groups of animals we administered the same number of whisker deflections but in a random rather than patterned fashion distributed either over 120 minutes or condensed into 10 minutes postpermanent middle cerebral artery occlusion. We also tested increased (full-whisker array versus single-whisker) stimulation. RESULTS: Early random whisker stimulation (condensed or dispersed) resulted in protection equivalent to early patterned stimulation. Early full-whisker array patterned stimulation also resulted in complete protection but promoted faster recovery. Late full-whisker array patterned stimulation, however, resulted in loss of evoked function and infarct volumes larger than those sustained by single-whisker counterparts. CONCLUSIONS: When induced early on after ischemic insult, stimulus-evoked cortical activity, irrespective of the parameters of peripheral stimulation that induced it, seems to be the important variable for neuroprotection.
BACKGROUND AND PURPOSE: Using a rodent model of ischemia (permanent middle cerebral artery occlusion), our laboratory previously demonstrated that 4.27 minutes of patterned single-whisker stimulation delivered over 120 minutes can fully protect from impending damage when initiated within 2 hours of permanent middle cerebral artery occlusion ("early"). When initiated 3 hours postpermanent middle cerebral artery occlusion ("late"), stimulation resulted in irreversible damage. Here we investigate the effect of altering pattern, distribution, or amount of stimulation in this model. METHODS: We assessed the cortex using functional imaging and histological analysis with altered stimulation treatment protocols. In 2 groups of animals we administered the same number of whisker deflections but in a random rather than patterned fashion distributed either over 120 minutes or condensed into 10 minutes postpermanent middle cerebral artery occlusion. We also tested increased (full-whisker array versus single-whisker) stimulation. RESULTS: Early random whisker stimulation (condensed or dispersed) resulted in protection equivalent to early patterned stimulation. Early full-whisker array patterned stimulation also resulted in complete protection but promoted faster recovery. Late full-whisker array patterned stimulation, however, resulted in loss of evoked function and infarct volumes larger than those sustained by single-whisker counterparts. CONCLUSIONS: When induced early on after ischemic insult, stimulus-evoked cortical activity, irrespective of the parameters of peripheral stimulation that induced it, seems to be the important variable for neuroprotection.
Authors: Daniel von Bornstädt; Thijs Houben; Jessica L Seidel; Yi Zheng; Ergin Dilekoz; Tao Qin; Nora Sandow; Sreekanth Kura; Katharina Eikermann-Haerter; Matthias Endres; David A Boas; Michael A Moskowitz; Eng H Lo; Jens P Dreier; Johannes Woitzik; Sava Sakadžić; Cenk Ayata Journal: Neuron Date: 2015-03-04 Impact factor: 17.173