The effects of atorvastatin on memory deficit and seizure susceptibility in pentylentetrazole-kindled rats

Deficits in memory function have been observed in pentylentetrazole (PTZ)-kindled rats. In the present study we examined the effects of atorvastatin ((3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitor) on PTZ kindling and related memory deficits in rats trained with the passive avoidance test. Subconvulsive PTZ doses rendered a gradual increase in seizure activity. PTZ kindling caused long-term memory to deteriorate. Atorvastatin per se and in PTZ-kindled rats improved learning and memory functions. It also prolonged latency (time to appearance of spike potentials) and diminished the amplitude and frequency of spike potentials, which indicate epileptic discharges. These novel findings suggest that the favorable effect of the atorvastatin on memory deficits provoked by PTZ kindling might be of clinical utility. (C) 2010 Elsevier Inc. All rights reserved

Effects of spermidine treatment on neurobehavioral development in intrauterine growth retarded (IUGR) rats

It was previously shown that polyamine treatment could induce precocious development of several somatic and neurobehavioral functions in newborn ruts. This study investigates the effects of daily injections of spermidine (SPMD) 50 mu l/10 g s.c. on neurobehavioral development of newborn rats experiencing undernutrition. Neurobehavioral development was assessed by measurements of gripping and righting reflexes. SPMD treated intrauterine growth retarded (IUGR) rats reached righting reflex control values at 30 days postnatal (1.87+/-0.78 s vs 1.75+/-0.66 s). Beginning from 7 days postnatal, gripping reflex values of SPMD treated IUGR rats declined. reaching that of controls at 30 days postnatal (1.77 +/- 91 degrees vs 1.82 +/- 65 degrees). These results suggest the utility of exogenous SPMD in rats experiencing undernutrition, thus indicating a clinical relevance. (C) 1999 Published by Elsevier Science Ltd. All rights reserved

Chronic nicotine pretreatment protects the blood-brain barrier against nicotine-induced seizures in the rat

This study was designed to investigate the possible protective actions of nicotine on cerebrovascular permeability in convulsions during nicotine-induced seizures. We have measured the permeability changes in the blood-brain barrier (BBB) macroscopically and spectrophotometrically by using Evans blue dye. Specific gravity measurements were also performed to assess brain edema which develops after blood-brain barrier opening. The experiments were carried out on Wistar rats. Rats were divided into two groups. They received acutely a convulsive dose of nicotine 3, 5, 8 and 9 mg kg(-1) i.p. or pretreated with a low dose of nicotine (0.8 mg kg(-1) i.p.) for 21 days followed by the procedure mentioned in the first group. Acute nicotine injection induced a significant increase in blood pressure and Evans-blue passage, despite a decline in specific gravity values. Low doses of chronic nicotine administration markedly reduced both the leakage of dye, and brain water content. Chronic treatment with low doses of nicotine (0.8 mg kg(-1) day(-1) s.c.) lessened the intensity of tonic-clonic seizures observed with a single dose of 3, 5, 8 or 9 mg kg-l nicotine. The data presented here demonstrate that nicotine pretreatment results in decreased sensitivity to nicotine-induced seizures in rats. (C) 1999 Academic Press

THE CEREBROVASCULAR PERMEABILITY AND EPILEPSY - THE ROLE OF BLOOD-PRESSURE

This study was designed to evaluate the role of elevated blood pressure on cerebrovascular permeability and brain tissue specific gravity during epileptic seizures induced by Pentylenetetrazole (PTZ). The experiments were carried out on Wistar rats. Specific gravity was measured bilaterally in 10 regional brain areas and Evans-blue passage (across blood-brain barrier) was spectrophotometrically measured in 6 brain areas. Animals were divided into four groups: they received i.v. either saline, 80mg/kg PTZ (convulsive dose), 40mg/kg PTZ (subconvulsive dose) or 80mg/kg PTZ+phentolamine. 80 mg/kg PTZ induced significantly an increase in blood pressure, in specific gravity and in Evans-blue passage. 40mg/kg PTZ induced an increase in blood pressure and caused small changes in specific gravity but not in Evans-blue passage. The last group, in which the rise in blood pressure was prevented with Phentolamine, also showed a significant increase in brain specific gravity and in Evans-blue passage. The results clearly show that the increased blood pressure may contribute to but is not entirely responsible for the changes in the cerebrovascular permeability induced by epileptic seizures

Erythropoietin prevents the increase in blood-brain barrier permeability during pentylentetrazol induced seizures

Recombinant human erythropoietin (r-Hu EPO) has been shown to exert neuroprotection in ischemic, excitotoxicity, trauma, convulsions and neurodegenerative disorders. Blood-brain barrier (BBB) leakage plays a role in the pathogenesis of many pathological states of the brain including neurodegenerative disorders. This study aimed to investigate the effects of r-Hu EPO on BBB integrity in pentylentetrazol (PTZ) induced seizures in rats. Seizures were observed and evaluated regard to latency and intensity for an hour. Macroscopical and spectrophotometrical measurement of Evans Blue (EB) leakage were observed for BBB integrity. r-Hu EPO was given intraperitoneally 24 h prior to seizure induction. Total seizure duration of 720 +/- 50 s after single PTZ administration (80 mg/kg i.p.) was declined to 190 40 s in r-Hu EPO pretreatment. A typical BBB breakdown pattern (i.e. staining in cerebellum, cerebral cortex, midbrain, hippocampus, thalamus and corpus striatum) was observed in rat brains with PTZ induced seizures; whereas, EPO pretreatment confined BBB leakage to cerebellum and cortical areas, and lessened the intensity of tonic-clonic seizures observed in PTZ seizures. The protective effect of r-Hu EPO on BBB permeability in seizures is a new and original finding. The protective action of r-Hu EPO in seizures and some of CNS pathologies warrant further investigations. (c) 2005 Elsevier Inc. All rights reserved

Long term consequences on spatial learning-memory of low-calorie diet during adolescence in female rats; hippocampal and prefrontal cortex BDNF level, expression of NeuN and cell proliferation in dentate gyrus.

Calorie restriction (CR) is argued to positively affect general health, longevity and normally occurring age-related reduction of cognition. Obesity during adolescence may adversely affect cognition in adulthood but, to date effects of CR have not been investigated. We hypothesized that feeding with as low as 15% low-calorie diet (LCD) during adolescence would increase hippocampal and prefrontal BDNF (Brain-derived neurotrophic factor) levels, proliferative cells and neuron numbers in dentate gyrus (DG), thus positively affecting spatial memory in adulthood. Spatial learning-memory function was improved in adult female Sprague Dawley rats fed with LCD during adolescence. PCNA (Proliferating cell nuclear antigen-cell proliferation marker) expressing cells and NeuN (Neuronal nuclear antigen-neuron marker) expressing cells in hippocampus DG which are critically involved in memory were increased. Hippocampus and prefrontal cortex BDNF levels were increased while serum glucose levels and level of lipid permddation indicator malondialdehyde in serum and hippocampus were reduced. Our unique results suggest that improved cognition in adult rats with LCD feeding during adolescence may result from the increase of neurogenesis and BDNF. These findings reveal the importance of nutrition in adolescence for cognitive function in adulthood. Our results may be useful for further studies aiming to treat age-related cognitive impairments. (C) 2015 Elsevier B.V. All rights reserved

Nitric oxide involvement in seizures elicited by pentylentetrazol and sex dependence

It has been known that susceptibility to some types of epilepsy is affected by sex. In addition, the role of NO in epileptogenesis is still unclear; NO has been suggested to be either an anticonvulsive or a proconvulsive agent. In an attempt to elucidate both the role of NO and sex differences in sensitivity to seizures, male and female Wistar rats were treated intraperitoneally (i.p.) by pentylentetrazol (PTZ)( 80 mg/kg) and by a nitric oxide synthase( NOS) inhibitor N-omega-nitro-L-arginine-mthylester(L-NAME)(50mg/kg) and a NO precursor sodium-nitroprusside (SNP) (2.5mg/kg)-applied 15 min. before PTZ injection. Latency, frequency, severity, and duration of generalized clonic and clonic-tonic convulsions were recorded. Furthermore, alterations in severity, latency, frequency, and duration of convulsions were observed to correlate with NO. Both sexes, injected with PTZ, showed repetitive seizure patterns. Seizures were found to be more severe in females. L-NAME and SNP pretreatment produced paradoxical effects on PTZ- induced seizures in both sexes. L-NAME completely prevented PTZ- induced seizures in male rats, whereas increased severity, frequency, duration, and significantly shortened the latency in female rats. Unexpectedly, SNP increased convulsion severity, frequency, duration, and shortened latencies in male, whereas it decreased convulsion severity, frequency, and duration and prolonged latency in females. These results indicate that endogenous NO is involved in the regulation of convulsive action suggesting a role depending on sex

Passage of spermidine across the blood-brain barrier in short recirculation periods following global cerebral ischemia: effects of mild hyperthermia

Transport of a polyamine (PA), spermidine (SPMD) into rat brain at various early postischemic periods was studied. Rats underwent 20 min of four-vessel occlusion (4VO) followed by 5, 10, 30 and 60 min of recirculation (RC) periods with natural brain temperature. H-3-aminoisobutyricacid (AIB) and C-14-SPMD were utilised to search dual functions of the blood-brain barrier (BBB); barrier and carrier functions, respectively. Unidirectional blood-to-brain transfer constant (Kin) was calculated for AM and SPMD in four brain regions-parieto-temporal cortex, striatum, hippocampus and cerebellum. Kin for SPMD ranged between 1.2 +/- 0.3 x 10(3) ml g(-1) min(-1) (for striatum) and 2.2 +/- 0.4 x 10(3) ml g(-1) min(-1) (for cerebellum) in controls. Kin for AIB showed similar values. At 5 and 10 min RC periods, Kin for both substances increased in a non-specific manner in all brain regions studied. In the cortex, Kin for SPMD at 5 and 10 min RC periods were 3.2 +/- 0.4 x 10(3) and 2.9 +/- 0.3 x 10(3) ml g(-1) min(-1), respectively, and found to be maximum with respect to other brain regions studied. 30 and 60 min RC groups showed specific transport for SPMD, whilst there were no changes for Kin for AIB, in all brain regions studied. Hippocampus showed the maximum increase in Kin SPMD at 60 min RC (2.7 +/- 0.3 x 10(3) ml g(-1) min(-1)), corresponding to a percentage rise of 121%. Intraischemic mild brain hyperthermia (39 degreesC) gave rise to a striking increase in Kin at 60 min postischemia for both substances. These results suggest that there is a specific transport of SPMD into brain at 30 and 60 min RC periods following 20 min of forebrain ischemia. Moreover, dual functions of the BBB were perturbed with intracerebral mild hyperthermia during ischemia. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved