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

2021 ◽  
Vol 8 (3) ◽  
pp. 216-228
Author(s):  
Se-Kwang Oh ◽  
Hyun-Jeong Park ◽  
Gyeong-Gyu Yu ◽  
Seong-Hae Jeong ◽  
Suk-Woo Lee ◽  
...  

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.

2021 ◽  
Vol 29 (4) ◽  
pp. 102-113
Author(s):  
Akbar Hajizadeh Moghaddam ◽  
◽  
Haniyeh Abbasalipour ◽  
Mojtaba Ranjbar ◽  
Sedigheh Khanjani Jelodar ◽  
...  

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.


2018 ◽  
Vol 8 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Hamidreza Famitafreshi ◽  
Morteza Karimian

Objective:Social isolation is associated with adverse effects on brain functions. According to previous studies, the reduction of oxidative stress improves cognitive functions. Memory performance is dependent on hippocampus and prefrontal function. The aim of this study is to show that impairment of memory in object recognition test in isolation state is accompanied by deregulation of oxidative stress balance in related areas.Methods and Materials:In this study, 14 male Sprague-Dawley rats were randomly divided into two groups as follows: social and isolation. Socialization and isolation plus one week of acclimatization occurred for fourteen days. At the end of the study, after performing behavioral test, (novel object recognition test) rats were anesthetized and sacrificed. After preparation of tissues in controlled condition, oxidative stress status in hippocampus and prefrontal cortex for Malondialdehyde (MDA), glutathione and nitrite/nitrate was assessed.Results:MDA in the hippocampus and prefrontal cortex was higher in isolated rats compared to social rats. Glutathione and nitrite/nitrate in the hippocampus and prefrontal cortex were lower in isolated rats compared to social rats. Memory performance in novel object recognition test both in short term and long term was better in social rats.Conclusion:Memory performance in novel object recognition test is influenced by social and oxidative stress status. So improving memory is possible through socialization and improvement of antioxidant status.


2019 ◽  
Vol 33 (12) ◽  
pp. 1610-1619 ◽  
Author(s):  
Lieve Desbonnet ◽  
Colm MP O’Tuathaigh ◽  
Clare O’Leary ◽  
Rachel Cox ◽  
Orna Tighe ◽  
...  

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.


2014 ◽  
Vol 272 ◽  
pp. 16-24 ◽  
Author(s):  
Jumpei Matsumoto ◽  
Takashi Uehara ◽  
Susumu Urakawa ◽  
Yusaku Takamura ◽  
Tomiki Sumiyoshi ◽  
...  

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