ABSTRACT
Objectives. Ischemic stroke is a leading cause of death and disability worldwide. To search for new therapeutic and pharmacotherapeutic strategies, numerous models of this disease have been proposed, the most popular being transient middle cerebral artery occlusion. Behavioral and sensorimotor testing, biochemical, and histological methods are traditionally used in conjunction with this model to assess the effectiveness of potential treatment options. Despite its wide overall popularity, electroencephalography/electrocorticography is quite rarely used in such studies. Materials and methods. In the present work, we explored the changes in brain electrical activity at days 3 and 7 after 30- and 45-min of transient middle cerebral artery occlusion in rats. Results. Cerebral ischemia altered the amplitude and spectral electrocorticogram characteristics, and led to a reorganization of inter- and intrahemispheric functional connections. Ischemia duration affected the severity as well as the nature of the observed changes. Conclusions. The dynamics of changes in brain electrical activity may indicate a spontaneous partial recovery of impaired cerebral functions at post-surgery day 7. Our results suggest that electrocorticography can be used successfully to assess the functional status of the brain following ischemic stroke in rats as well as to investigate the dynamics of functional recovery.
ABSTRACT
The search for and development of new neuroprotective (or cerebroprotective) drugs, as well as suitable methods for their preclinical efficacy evaluation, are priorities for current biomedical research. Alpha-2 adrenergic agonists, such as mafedine and dexmedetomidine, are a highly appealing group of drugs capable of reducing neurological deficits which result from brain trauma and vascular events in both experimental animals and human patients. Thus, our aim was to assess the effects of mafedine and dexmedetomidine on the brain's electrical activity in a controlled cortical-impact model of traumatic brain injury (TBI) in rats. The functional status of the animals was assessed by electrocorticography (ECoG), using ECoG electrodes which were chronically implanted in different cortical regions. The administration of intraperitoneal mafedine sodium at 2.5 mgâkg-1 at 1 h after TBI induction, and daily for the following 6 days, restored interhemispheric connectivity in remote brain regions and intrahemispheric connections within the unaffected hemisphere at post-TBI day 7. Animals that had received mafedine sodium also demonstrated an improvement in cortical responses to photic and somatosensory stimulation. Dexmedetomidine at 25 µgâkg-1 did not affect the brain's electrical activity in brain-injured rats. Our results confirm the previously described neuroprotective effects of mafedine sodium and suggest that ECoG registration and analysis are a viable method evaluating drug efficacy in experimental animal models of TBI.
ABSTRACT
Pharmacological agents acting at alpha-2 adrenergic receptors are widely used in physiology and neuroscience research. Mounting evidence of their potential utility in clinical and experimental psychopharmacology, necessitates new models and novel model organisms for their screening. Here, we characterize behavioral effects of mafedine (6-oxo-1-phenyl-2- (phenylamino)-1,6-dihydropyrimidine-4-sodium olate), a novel drug with alpha-2 adrenergic receptor agonistic effects, in adult zebrafish (Danio rerio) in the novel tank test of anxiety and activity. Following an acute 20-min exposure, mafedine at 60 mg/L produced a mild psychostimulant action with some anxiogenic-like effects. Repeated acute 20-min/day administration of mafedine for 7 consecutive days at 1, 5 and 10 mg/L had a similar action on fish behavior as an acute exposure to 60 mg/L. Since mafedine demonstrated robust behavioral effects in zebrafish - a sensitive vertebrate aquatic model, it is likely that it may modulate rodent and human behavior as well. Thus, further studies are needed to explore this possibility in detail, and whether it may foster clinical application of mafedine and related alpha-2 adrenergic agents.
