Effect of low­frequency repetitive transcranial magnetic stimulation on cognitive function in rats with medial temporal lobe epilepsy.

Epilepsy, especially the medial temporal lobe epilepsy (TLE), can result in cognitive impairment. Low­frequency repetitive magnetic stimulation (rTMS) has been verified to suppress neural excitability and reduce seizures. Given its potential in modifying cortical activity, we aimed to investigate its impact on cognitive function in the context of epilepsy, a condition where the use of rTMS has not been extensively explored. However, the influence on cognitive function has not yet been investigated. Therefore, this study aimed to investigate the effects of low­frequency rTMS on cognitive improvement in epileptic rats. Rats used in this study were randomly divided into five groups: the sham group, the epilepsy group, and three epilepsy groups treated with rTMS at different frequencies. Each group underwent the Morris water maze test to investigate hippocampus­dependent episodic memory, to evaluate their cognitive performance. Further assessments included patch clamp and western blot techniques to estimate the synaptic function in the hippocampus. Comparison between groups showed that low­frequency rTMS significantly reduced spontaneous recurrent seizures and improved spatial learning and memory impairment in epileptic rats. Additionally, rTMS remodeled the synaptic plasticity affected by seizures and notably enhanced the expression of AMPAR and synaptophysin. Low­frequency rTMS can antagonize the cognitive impairment caused by TLE, and promote synaptic connections.

[Acute Myocardial Infarction and Purpuric Drug Eruption Caused by Erlotinib Combined with Cabozantinib:Report of One Case].

Multi-target anticancer drugs have a more comprehensive and extensive range of action,and there is an uncertain risk in the combination of two drugs.A case of acute toxicity induced by erlotinib combined with cabozantinib is reported in this article.

Uremic encephalopathy with isolated brainstem involvement revealed by magnetic resonance image: a case report.

BACKGROUND: Uremic Encephalopathy (UE) is a neurological complication associated with acute or chronic renal failure. Imaging findings of UE may present involvement of the basal ganglia, cortical or subcortical regions, and white matter. We report a rare case of UE caused by neurogenic bladder with isolated brainstem involvement revealed by magnetic resonance imaging (MRI). Immediate therapy resulted in full recovery of neurological signs and changes on MRI. CASE PRESENTATION: A 14-year-old Han Chinese woman with a history of chronic renal failure caused by neurogenic bladder. On admission, she was unconscious and her pupils presented different sizes, while her vital signs were normal. MRI showed high signal in the dorsal pontine base and in the mid brain on fluid-attenuated inversion-recovery (FLAIR) imaging and on T2-weighted imaging while the signal was normal on diffusion-weighted images (DWI). Blood analysis revealed renal failure and acidosis. After urinary retention treatment and acidosis correction, the patient soon recovered. Follow-up MRI 2 months after the discharge revealed complete resolution of UE in the brainstem. CONCLUSION: We reported a rare case of a patient with UE that had unusual imaging manifestations for whom timely diagnosis and treatment assured recovery.

Astaxanthin rescues neuron loss and attenuates oxidative stress induced by amygdala kindling in adult rat hippocampus.

Oxidative stress plays an important role in the neuronal damage induced by epilepsy. The present study assessed the possible neuroprotective effects of astaxanthin (ATX) on neuronal damage, in hippocampal CA3 neurons following amygdala kindling. Male Sprague-Dawley rats were chronically kindled in the amygdala and ATX or equal volume of vehicle was given by intraperitoneally. Twenty-four hours after the last stimulation, the rats were sacrificed by decapitation. Histopathological changes and the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and reduced glutathione (GSH) were measured, cytosolic cytochrome c (CytC) and caspase-3 activities in the hippocampus were also recorded. We found extensive neuronal damage in the CA3 region in the kindling group, which was preceded by increases of ROS level and MDA concentration and was followed by caspase-3 activation and an increase in cytosolic CytC. Treatment with ATX markedly attenuated the neuronal damage. In addition, ATX significantly decreased ROS and MDA concentrations and increased GSH levels. Moreover, ATX suppressed the translation of CytC release and caspase-3 activation in hippocampus. Together, these results suggest that ATX protects against neuronal loss due to epilepsy in the rat hippocampus by attenuating oxidative damage, lipid peroxidation and inhibiting the mitochondrion-related apoptotic pathway.

Environmental enrichment restores cognitive deficits induced by prenatal maternal seizure.

Maternal seizure has adverse effects on brain histology as well as on learning and memory ability in progeny. An enriched environment (EE) is known to promote structural changes in the brain and improve cognitive and motor deficits following a variety of brain injuries. Whether EE treatment in early postnatal periods could restore cognitive impairment induced by prenatal maternal seizure is unknown. Adult female Sprague-Dawley rats were randomly separated into two groups and were injected intraperitoneally either saline or pentylenetetrazol (PTZ) for 30 days. Then the fully kindled rats and control animals were allowed to mate. PTZ administration was continued until delivery, while the control group received saline at the same time. After weaning at postnatal day 22, one-half of the male offspring in the control and in the prenatal maternal group were given the environmental enrichment treatment through all the experiments until they were tested. Morris water maze testing was performed at 8 weeks of age. Western blot and synaptic ultrastructure analysis were then performed. We found that EE treatment reversed spatial learning deficits induced by prenatal maternal seizure. An EE also reversed the changes in synaptic ultrastructure following prenatal maternal seizure. In addition, prenatal maternal seizure significantly decreased phosphorylation states of cAMP response element binding (CREB) in the hippocampus, whereas EE reversed this reduced expression. These findings suggest that EE treatment on early postnatal periods could be a potential therapy for improving cognitive deficits induced by prenatal maternal seizure.

Effects of epigallocatechin-3-gallate on pentylenetetrazole-induced kindling, cognitive impairment and oxidative stress in rats.

Cognitive dysfunction is commonly observed in epileptic patients. It has been shown that not only epilepsy but also antiepileptic drugs could induce cognitive impairment. Thus, there is an urgent need for drugs that can suppress seizures without causing cognitive deficit. Recent studies have shown that oxidative stress is involved in the pathophysiology of epilepsy, and many antioxidants have an antiepileptic property. Epigallocatechin-3-gallate (EGCG), a catechin polyphenols component, is found to be an effective antioxidant. The purpose of this study was to assess the effect of EGCG against seizures, seizure-induced oxidative stress and cognitive impairment in pentylenetetrazole-induced kindling. Male Sprague-Dawley rats were injected intraperitoneally with a dose of 35 mg/kg of pentylenetetrazole (PTZ) once every alternate day for 13 injections. EGCG was administered daily in two doses (25mg/kg and 50mg/kg) intraperitoneally along with alternate-day PTZ. Morris water maze test was carried out 24h after the last injection of PTZ, and the oxidative stress parameters (malondialdehyde and glutathione) were assessed after the completion of the behavioral test. The results showed that EGCG dose-dependently suppressed the progression of kindling. EGCG also ameliorated the cognitive impairment and oxidative stress induced by PTZ kindling. These observations suggest that EGCG may be a potential agent for the treatment of epilepsy as well as a preventive agent against cognitive impairment induced by seizure.

Memantine attenuates the impairment of spatial learning and memory of pentylenetetrazol-kindled rats.

Cognitive disorders after epilepsy can have a great impact on the quality of life of epileptic patients, though it has not drawn much attention. Even after identified, it is often undertreated or has gone untreated. Memantine has been approved to treat moderate to severe Alzheimer disease (AD), which is characterized by cognitive impairment. In present study, we determined the effects of memantine on PTZ-kindled rats, which can mimic the postseizure dysfunction that resembles symptoms observed in human epilepsy. We found that memantine can ameliorate the spatial learning and memory of epileptic rats. But contrary to previous claims that memantine can improve cognition in AD patients, without serious side effects on normal learning and memory abilities, we found that rats treated only with memantine exhibited the impaired spatial learning and memory ability. We conclude that memantine can improve cognition related to an excitotoxicity-induced pathologic state, but the potential side effects of memantine on the physiological processes should be considered.

[Effects of anisodamine on microcirculation of the asystole rats during the cardiopulmonary resuscitation].

OBJECTIVE: To study the effects of anisodamine (Ani) on microcirculation and reperfusion volume of intestine wall in Wistar rats during cardiopulmonary resuscitation (CPR) for cardiac arrest (CA). METHODS: Healthy Wistar rats subjected to CA and resuscitation were randomly divided into four groups, 15 rats in each group. After a 4-minute-non-intervention interval, CPR was started. After CPR for 4 minutes the animals in control group received normal saline, group epinephrine (Epi) received Epi (bolus dose of 200 microg/kg), Epi plus low dosage Ani (Ld Ani) group received Epi plus Ani (bolus dose of 200 microg/kg Epi followed by Ani of 5 mg/kg), and Epi plus high dosage Ani (Hd Ani) group received Epi plus Ani (bolus dose of 200 microg/kg Epi followed by Ani of 10 mg/kg). The recanalization rate of mesenteric arterioles and venules, caliber of the recanalized mesentery arteriole and venule, and the reperfusion volume of intestine wall were observed in vivo in rats with restoration of spontaneous circulation (ROSC). RESULTS: As the rate of recanalization of mesenteric arterioles and venules was compared, group Hd Ani (66.6%, 60.0%)>group Ld Ani (60.0%, 53.3%)>group control (40.0%, 40.0%)>group Epi (26.7%, 20.0%), and group Ld Ani and group Hd Ani was much better than group Epi(all P<0.05). When the caliber of arterioles and venules was compared, group Hd Ani>group Ld Ani>group control>group Epi 30 minutes and 60 minutes after ROSC. Thirty minutes after ROSC, the caliber of arterioles and venules was much larger in group Ld Ani and group Hd Ani than that in group Epi (all P<0.05). Sixty minutes after ROSC, there was no statistical difference in the caliber of venules between group Ld Ani and group Epi, so as between group Ld Ani and group Hd Ani. Reperfusion volume of intestine wall in group Ld Ani and group Hd Ani was higher than that in groups control and Epi 15 minutes after ROSC, and it kept on to be better up to 60 minutes after ROSC. CONCLUSION: Administration of Ani at earlier period of resuscitation could improve microcirculation of the tissue and raise ROSC rate and successful rate of resuscitation.