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Stroke is despite of progressive improvements in treatment and reperfusion strategies one of the most devastating human pathology. However, as quality of acute health care improves and more people survive ischemic attack, healthcare specialists have to solve new challenges to preserve reasonable quality of life to these patients. Thus, novel approaches which prevents comorbidities of stroke and improve quality of life of stroke survivors in general has to be developed and experimentally tested. The aim of the present paper was to establish reliable rat model of middle cerebral occlusion and set of methods allowing selection of animals suitable for long-term experiments. We have compared mortality rates, cerebral blood flow and extension of ischemic lesion induced by intraluminal filament in three widely used outbred rat strains. We have additionally used an animal 18F-DG PET scans to verify its reliability in noninvasive detection of ischemic infarct in acute period (24 h after MCAO) for selecting animals eligible for long survival experiments. Our data clearly indicates that high variability between rat strains might negatively influence stroke induction by intraluminal thread occlusion of middle cerebral artery. Most reliable outbred rat strain in our hands was Sprague-Dawley where maximal reduction of cerebral blood flow and extensive ischemic lesion was observed. Contrary, Wistar rats exhibited higher mortality and Long-Evans rats significantly smaller or no ischemic region in comparison to Sprague-Dawley. Additionally, we have confirmed a positron emission tomography with 18F-fluorodeoxyglucose as suitable method to assess extension of ischemic region in acute period after the experimental arterial occlusion in rats. [ABSTRACT FROM AUTHOR]

The role of brain derived nitric oxide in the physiology and behavior remains disputable. One of the reasons of the controversies might be systemic side effects of nitric oxide synthase inhibitors. Therefore, under nNOS inhibition by 7- nitroindazole (7-NI) we carried out recordings of blood gasses, blood pressure and spontaneous EEG in conscious adult rats. Locomotion and spontaneous behavior were assessed in an open field. In addition skilled walking and limb coordination were evaluated using a ladder rung walking test. The blood gas analysis revealed a significant increase in pC02 180 min and 240 min after the application of 7-NI. The power and entropy decreased simultaneously with a shift of the mean frequency of the spontaneous EEG toward slow oscillations after 7-NI treatment. The thresholds of evoked potentials underwent a significant drop and a trend towards a slight increase in the 1-0 curve slope was observed. 7-NI significantly suppressed open field behavior expressed as distance moved, exploratory rearing and grooming. As for the ladder rung walking test the 7-NI treated animals had more errors in foot placement indicating impairment in limb coordination. Therefore our findings suggest that 7-NI increased cortical excitability and altered some physiological and behavioral parameters. [ABSTRACT FROM AUTHOR]

The role of neuronal nitric oxide synthase (nNOS) in the pathophysiology of epilepsy and seizures remains disputable. One of the reasons why results from the acute in vivo studies display controversies might be the effect on the regulation of cerebral blood flow (CBF) during pharmacologically induced alterations of NO system. We examined neurovascular coupling in the rat sensorimotor cortex in response to transcallosal stimulation under nNOS inhibition by 7-nitroindazole (7-NI). Adult Wistar rats were anesthetized with urethane and epidural silver EEG electrodes were implanted over sensorimotor cortices. Regional CBF was measured by Laser Doppler Flowmetry (LDF). We catheterized a common carotid artery to measure arterial blood pressure (BP). 7-NI did not significantly affect blood pressure and heart rate. Electrophysiological recordings of evoked potentials (EPs) revealed no effect on their amplitude, rhythmic potentiation or depression of EPs. Transcallosal stimulation of the contralateral cortex induced a frequency dependent rise in CBF. Although 7-NI did not significantly affect basal CBF and cortical excitability, hemodynamic responses to the transcallosal stimulation were diminished implicating a role of nNOS in neurovascular coupling. Urethane anesthesia is suitable for future epileptological experiments. Our findings demonstrate that NO contributes to the hemodynamic response during brain activation. [ABSTRACT FROM AUTHOR]

Abstract: Perinatal stroke is a common cerebrovascular disorder affecting 1 in every 4000 births; typically associated with epilepsy. We sought to determine seizure susceptibility to pentylentetrazol (PTZ)-induced seizures in developing rats with a history of photothrombotic lesion of sensorimotor cortex induced at postnatal day 7. Lesioned animals were tested at P12 or P25 and compared with sham-operated controls. Three models of epileptic seizures were elicited by PTZ: episodes of spike-and-wave rhythm, minimal clonic seizures and generalized tonic–clonic seizures. PTZ (60 and 100mg/kg) was administered subcutaneously to assess seizure occurrence, latency and severity. In addition, episodes of rhythmic EEG activity were analyzed at P25 following successive interperitoneal 20 and 40mg/kg PTZ administration. There was only one significant change in convulsive seizures—decreased latency of generalized seizures in lesioned 12-day-old animals. EEG study demonstrated marked difference between lesioned and control rats. Lesioned rats had longer latencies and longer durations of the first rhythmic episode (following 20mg/kg PTZ) as compared to controls. After 40mg/kg of PTZ, 7 in 8 leisioned and 1 in 8 control rats exhibited clonic seizures. Cortical ischemic lesion during early development affected differently the susceptibility of rat's brain to three types of PTZ-induced seizures 5 and 18 days post photothrombotic insults. [Copyright &y& Elsevier]

Endothelin-1 (ET-1) is a neuroactive protein produced in most brain cell types and participates in regulation of cerebral blood flow and blood pressure. In addition to its vascular effects, ET-1 affects synaptic and nonsynaptic neuronal and glial functions. Direct application of ET-1 to the hippocampus of immature rats results in cerebral ischemia, acute seizures, and epileptogenesis. Here, we investigated whether ET-1 itself modifies the excitability of hippocampal and cortical circuitry and whether acute seizures observed in vivo are due to nonvascular actions of ET-1. We used acute hippocampal and cortical slices that were preincubated with ET-1 (20 µM) for electrophysiological recordings. None of the slices preincubated with ET-1 exhibited spontaneous epileptic activity. The slope of the stimulus intensity-evoked response (input-output) curve and shape of the evoked response did not differ between ET-1-pretreated and control groups, suggesting no changes in excitability after ET-1 treatment. The threshold for eliciting an evoked response was not significantly increased in either hippocampal or cortical regions when pretreated with ET-1. Our data suggest that acute seizures after intrahippocampal application of ET-1 in rats are likely caused by ischemia rather than by a direct action of ET-1 on brain tissue. [ABSTRACT FROM AUTHOR]