Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact

Objective Hypoxic ischemia (HI) is a secondary insult that can cause fatal neurologic outcomes after traumatic brain injury (TBI), ranging from mild cognitive deficits to persistent vegetative states. We here aimed to unravel the underlying pathological mechanisms of HI injury in a TBI mouse model.Methods Neurobehavior, neuroinflammation, and oxidative stress were assessed in a mouse model of controlled cortical impact (CCI) injury followed by HI. Mice underwent CCI alone, CCI followed by HI, HI alone, or sham operation. HI was induced by one-vessel carotid ligation with 1 hour of 8% oxygen in nitrogen. Learning and memory were assessed using the novel object recognition test, contextual and cued fear conditioning, and Barnes maze test. Brain cytokine production and oxidative stress-related components were measured.Results Compared to TBI-only animals, TBI followed by HI mice exhibited significantly poorer survival and health scores, spatial learning and memory in the Barnes maze test, discrimination memory in the novel object recognition test, and fear memory following contextual and cued fear conditioning. Malondialdehyde levels were significantly lower, whereas glutathione peroxidase activity was significantly higher in TBI followed by HI mice compared to TBI-only and sham counterparts, respectively. Interleukin-6 levels were significantly higher in TBI followed by HI mice compared to both TBI-only and sham animals.Conclusion Post-traumatic HI aggravated deficits in spatial, fear, and discrimination memory in an experimental TBI mouse model. Our results suggest that increased neuroinflammation and oxidative stress contribute to HI-induced neurobehavioral impairments after TBI.

Cnidoscolus aconitifolius-supplemented diet enhanced neurocognition, endogenous antioxidants and cholinergic system and maintains hippocampal neuronal integrity in male Wistar rats

Objectives Cnidoscolus aconitifolius have been investigated to have abundant phytochemicals. However, study on the effect of Cnidoscolus aconitifolius on neurobehavioral performance when supplemented with diet is lacking. The study is aimed at investigating the memory-enhancing effect of Cnidoscolus aconitifolius-supplemented diet (CAD) using Morris water maze and Novel object recognition test. Methods Ninety male Wistar rats (80–100 g) were fed with CAD (1, 2.5, 5 and 10%) continuously for a period of 4, 8 and 12 weeks respectively. Six animals per group were used for assessment of memory performance (Morris water maze [MWM] and Novel object recognition test [NORT]); afterwards the brain tissues were harvested for malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) estimation. Acetylcholinesterase (AChE) concentration was also determined. Hippocampal architectural change in the neuron was examined using hematoxylin and eosin (H&E) and cresyl fast violet (Nissl) stain. Results Higher percentage of CAD significantly (p<0.05) improve memory performance with time-dependent effects in rats fed with CAD on MMW and NORT. MDA significantly (p<0.05) reduce in 1 and 2.5% CAD groups at 4th weeks and in 2.5 and 5% CAD groups at 8th weeks while GSH concentration significantly (p<0.05) increase at 12th weeks in 2.5 and 10% CAD groups. However, CAT concentration significantly (p<0.05) increase in 2.5, and 5%, CAD groups, 1, 5, and 10% CAD groups and in 5, and 10% CAD groups at 4th, 8th and 12th weeks. AChE significantly (p<0.05) reduce at 4th and 12th weeks. Histological assessment reveals no neuronal and pyramidal degeneration (chromatolysis) at the hippocampal Cornu Ammonis 3 (CA3) region. Conclusions The results suggest that CAD boost memory performance in rats through positive modulation of oxidative stress, cholinergic system and degeneration of hippocampal neurons.

Effect of Sumac Nano-phytosome on Memory and Oxidative Stress in Valproic Acid-induced Rat Model of Autism Spectrum Disorder

Background: Autism Spectrum Disorder (ASD) is an advanced neurological disorder characterized by symptoms such as deficits in social interaction, communication, and cognition. Although sumac fruit contains compounds with antioxidant and anti-inflammatory properties, its effectiveness is limited due to its low bioavailability. Objective: This study aims to investigate the neuroprotective effect of sumac extract and sumac nano-phytosome on memory and oxidative stress in the hippocampal area of ASD rats. Materials and Methods: In this experimental study, pregnant female rats were first divided into healthy and patient groups. In the patient group, 500 mg/kg body weight valproic acid was injected intraperitoneally on day 12.5 of pregnancy. Male rats born in the healthy group were further divided into two healthy control and positive control groups, and those in the patient group were divided into two treatment groups of Sumac Extract (n=6) and Sumac Nano-Phytosome (n=6) 21 days after birth. The control groups received only saline, while treatment groups received SE and SNP (40 mg/kg/PO) for 4 weeks. Novel object recognition test was performed to assess recongnition memory of rats on day 49 after birth. Finally, Total Antioxidant Capacity (TAC), Glutathione Peroxidase (GPx), Glutathione Reductase (GRx) and Catalase (CAT) were measured in the hippocampus of rats. Results: Valproic acid significantly decreased the discrimination index in novel object recognition test as well as GPx, GRx and CAT, and TAC levels in the hippocampus (P<0.001). Treatment with sumac nano-phytosome significantly improved the memory and the activity of antioxidant enzymes (GPx, GRx and CAT) and TAC (P<0.001). Conclusion: Sumac nano-phytosome can improve memory deficits and oxidative stress more compared to sumac extract in ASD rats due to increased bioavailability.

Rosuvastatin Improves Cognitive Function of Chronic Hypertensive Rats by Attenuating White Matter Lesions and Beta-Amyloid Deposits

Hypertensive white matter lesion (WML) is one of common causes of vascular cognitive impairment. In this study, we aimed to investigate the effect of rosuvastatin on cognitive impairment and its underlying mechanisms in chronic hypertensive rats. From the 8th week after establishment of stroke-prone renovascular hypertensive rats (RHRSPs), rosuvastatin (10 mg/kg) or saline as a control was administrated once daily for consecutive 12 weeks by gastric gavage. Cognitive function was assessed with the Morris water maze test and novel object recognition test. WML was observed by Luxol fast blue staining. Aβ deposits, Claudin-5, Occludin, and ZO-1 were determined by immunofluorescence. After rosuvastatin treatment, the escape latencies were decreased and the time of crossing the hidden platform was increased in the Morris water maze, compared with the vehicle-treated RHRSP group. In a novel object recognition test, the recognition index in the rosuvastatin-treated RHRSP group was significantly larger than that in the vehicle-treated RHRSP group. Rosuvastatin treatment presented with the effects of lower WML grades, higher expression of tight junction proteins Claudin-5, Occludin, and ZO-1 in the corpus callosum, and less Aβ deposits in the cortex and hippocampus. The data suggested that rosuvastatin improved the cognitive function of chronic hypertensive rats partly by attenuating WML and reducing Aβ burden.

Acute stress in adolescence vs early adulthood following selective deletion of dysbindin-1A: Effects on anxiety, cognition and other schizophrenia-related phenotypes

Background: As exposure to stress has been linked to the onset and maintenance of psychotic illness, its pathogenesis may involve environmental stressors interacting with genetic vulnerability. Aim: To establish whether acute stress interacts with a targeted mutation of the gene encoding the neurodevelopmental factor dystrobrevin-binding protein 1 (DTNBP1), resulting in a specific loss of the isoform dysbindin-1A, to influence schizophrenia-relevant phenotypes in mice during adolescence and adulthood. Methods: Male and female mice with a heterozygous or homozygous deletion of DTNBP1 were assessed in the open field test following acute restraint stress in adolescence (Day 35) and young adulthood (Day 60–70). Effects of acute restraint stress on memory retention in the novel object recognition test was also assessed in adulthood. Baseline corticosterone was measured in serum samples and, brain-derived neurotrophic factor (BDNF), glucocorticoid and mineralocorticoid receptor gene expression levels were measured in the hippocampus of adult mice. Results: In the open field, deletion of dysbindin-1A induced hyperactivity and attenuated the action of stress to reduce hyperactivity in adolescence but not in adulthood; in females deletion of dysbindin-1A attenuated the effect of acute stress to increase anxiety-related behaviour in adolescence but not in adulthood. In the novel object recognition test, deletion of dysbindin-1A impaired memory and also revealed an increase in anxiety-related behaviour and a decrease in hippocampal BDNF gene expression in males. Conclusions: These data suggest that deletion of dysbindin-1A influences behaviours related to schizophrenia and anxiety more robustly in adolescence than in adulthood and that dysbindin-1A influences stress-related responses in a sex-dependent manner.

Kompleksitas Obyek dan Running-Wheel Mempengaruhi Novel Object Recognition Test pada Mencit (Mus musculus)

This research aimed to confirm the tendency of mice to novel object, effect of exercise (in running-wheel) toward memory of mice and to test tendency of mice in avoiding predator signal in novel object. Novel object recognition test (NORT) used to test the memory the day after acquisition phase (NORT I) and memory one week after exercise was given (running-wheel) (NORT II). The result showed that there was no tendency of mice in exploring toward novel object in both NORT I and NORT II. This might happen because the complexity of familiar object higher than novel object, so the familiar object could accommodate more activities. Exercise using running-wheel in mice had an effect on memory, it could be seen in decreasing duration of object exploration time from NORT I to NORT II. There was no tendency in avoiding predator’s signal on novel object which was attached by urine addition (odor signal).