scholarly journals Molecular Targeting of Nrf2 and NFkB Signaling by 3-acetyl-11-keto- β-boswellic Acid and Piperine in Fluid Percussion Rat Model of Traumatic Brain Injury

2021 ◽  
Author(s):  
Satyabrata Kundu ◽  
Shamsher Singh
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuroprotective Effect ◽  
Histopathological Analysis ◽  
Cortical Region ◽  
Boswellic Acid ◽  
Fluid Percussion ◽  
Fluid Percussion Injury ◽  
Behavioral Parameters ◽  
Anti Inflammatory

Abstract Background & purpose: Traumatic brain injury in rats through lateral fluid percussion injury (LFPI) causes elevation in intracranial pressure which leads to impairments in motor and cognitive behavior. 3-acetyl-11-keto-β-boswellic acid (AKBA) is a well-known anti-inflammatory agent but it has very low bioavailability. The current study was established to investigate the neuroprotective effect of AKBA in combination with bioenhancer piperine in LFPI induced TBI experimental rats.Experimental approach: Fluid percussion injury was created by delivering 50 mmHg of pressure for 3 minutes to the exposed brain. AKBA 25 mg/kg and 50 mg/kg orally and AKBA ((25 mg/kg, p.o.) in combination with piperine (2.5 mg/kg, p.o.) was administered from day 1 to day 14. On 1st, 7th and 14th day, the behavioral parameters were checked. On 15th day, animals were euthanized. Then the cortex was isolated for the estimation of biochemical levels (MDA, nitrite, reduced GSH, catalase), neuroinflammatory markers (TNF-α, IL-1β, IL-6), and neurotransmitters (norepinephrine, dopamine, 5-HT, GABA, glutamate). From some animals, hippocampus and cortex were isolated for histopathological analysis and expressions of Nrf2 and NFkB was measured by immunohistological study. Key results: Treatment with AKBA significantly attenuated LFPI induced abnormalities, biochemical and neurotransmitter changes in experimental rats. Further finding AKBA in combination with piperine significantly prevented histopathological changes, increased Nrf2 positive cells and reduced NFkB expression in the cortical region. Conclusion & implication: The present study concluded that AKBA along with piperine achieved anti-oxidant, anti-inflammatory, neuromodulatory effects as well as prevented neuronal injury via targeting Nrf2 and NFkB.

scholarly journals Hypothermia Attenuates the Loss of Hippocampal Microtubule-Associated Protein 2 (MAP2) following Traumatic Brain Injury

1993 ◽  
Vol 13 (5) ◽  
pp. 796-802 ◽  
Author(s):  
William C. Taft ◽  
Keyi Yang ◽  
C. Edward Dixon ◽  
Guy L. Clifton ◽  
Ronald L. Hayes
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Causal Link ◽  
Moderate Hypothermia ◽  
Post Injury ◽  
Protein Levels ◽  
Fluid Percussion ◽  
Fluid Percussion Injury ◽  
Neurobehavioral Deficits ◽  
Normothermic Group

Traumatic brain injury (TBI) produces a tissue-specific decrease in protein levels of microtubule-associated protein 2 (MAP2), an important cross-linking component of the neuronal cytoskeleton. Because moderate brain hypothermia (30°C) reduces certain neurobehavioral deficits produced by TBI, we examined the efficacy of moderate hypothermia (30°C) in reversing the TBI-induced loss of MAP2 protein. Naive, sham-injured, and moderate (2.1 atm) fluid percussion-injured rats were assessed for MAP2 protein content 3 h post injury using quantitative immunoreactivity measurements. Parallel groups of sham-injured and fluid percussion-injured animals were maintained in moderate hypothermia (30°C), as measured by temporalis muscle temperature, for MAP2 quantitation 3 h post injury. No difference in MAP2 levels was observed between naive and sham-injured normothermic animals. Hypothermia alone had no effect on soluble MAP2 levels in sham-injured animals compared with normothermic sham-injured controls (88.0 ± 7.3%; p > 0.10). Fluid percussion injury dramatically reduced MAP2 levels in he normothermic group (44.3 ± 5.9%; p < 0.0005) compared with normothermic sham-injured controls. No significant reduction of MAP2 was seen in the hypothermic injured group (95.2 ± 4.6%; compared with hypothermic sham-injured controls, p > 0.20). Although it is premature to infer any causal link, the data suggest that the attenuation of injury-induced MAP2 loss by hypothermia may contribute to its overall neuroprotective action.

Possible protective effect of endogenous opioids in traumatic brain injury

1990 ◽  
Vol 72 (2) ◽  
pp. 252-261 ◽  
Author(s):  
Ronald L. Hayes ◽  
Bruce G. Lyeth ◽  
Larry W. Jenkins ◽  
Richard Zimmerman ◽  
Tracy K. McIntosh ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Body Weight ◽  
Brain Injury ◽  
Endogenous Opioids ◽  
Neurological Deficits ◽  
Content Type ◽  
Fluid Percussion ◽  
Fluid Percussion Injury ◽  
Drug Treatments

✓ Naloxone (0.1, 1.0, or 20.0 mg/kg), morphine (1.0 or 10.0 mg/kg), or saline was administered systemically intraperitoneally to rats 15 minutes prior to moderate fluid-percussion brain injury. The effects of the drugs were measured on systemic physiological, neurological, and body-weight responses to injury. The animals were trained prior to injury and were assessed for 10 days after injury on body-weight responses and neurological endpoints. Low doses of naloxone (0.1 or 1.0 mg/kg) significantly exacerbated neurological deficits associated with injury. Morphine (10.0 mg/kg) significantly reduced neurological deficits associated with injury. The drugs had no effect on neurological measures or body weight in sham-injured animals. Drug treatments did not significantly alter systemic physiological responses to injury. Data from these experiments suggest the involvement of endogenous opioids in at least some components of neurological deficits following traumatic brain injury and suggest the possibility that at least some classes of endogenous opioids may protect against long-term neurological deficits produced by fluid-percussion injury to the rat.

A rapid lateral fluid percussion injury rodent model of traumatic brain injury and post-traumatic epilepsy

Neuroreport ◽  
2014 ◽  
pp. 1 ◽  
Author(s):  
Mustafa Q. Hameed ◽  
Grant S. Goodrich ◽  
Sameer C. Dhamne ◽  
Asa Amandusson ◽  
Tsung-Hsun Hsieh ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rodent Model ◽  
Fluid Percussion ◽  
Fluid Percussion Injury ◽  
Post Traumatic ◽  
Lateral Fluid Percussion ◽  
Post Traumatic Epilepsy ◽  
Traumatic Epilepsy

scholarly journals Importance of Posttraumatic Hypothermia and Hyperthermia on the Inflammatory Response after Fluid Percussion Brain Injury: Biochemical and Immunocytochemical Studies

2000 ◽  
Vol 20 (3) ◽  
pp. 531-542 ◽  
Author(s):  
Katina Chatzipanteli ◽  
Ofelia F. Alonso ◽  
Susan Kraydieh ◽  
W. Dalton Dietrich
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Cortical Region ◽  
Myeloperoxidase Activity ◽  
Fluid Percussion ◽  
Moderate Traumatic Brain Injury ◽  
Activity Temperature ◽  
Series Of Experiments ◽  
Subcortical Regions

The purpose of this study was to investigate: 1) the temporal and regional profile of polymorphonuclear leukocyte (PMNL) infiltration after moderate traumatic brain injury using the parasagittal fluid percussion model and 2) the effects of posttraumatic hypothermia (30°C) and hyperthermia (39°C) on the acute and subacute inflammatory response. We hypothesized that posttraumatic hypothermia would reduce the degree of PMNL accumulation whereas hyperthermia would exacerbate this response to injury. In the first series of experiments we quantitated the temporal profile of altered myeloperoxidase activity under normothermic (37°C) conditions (n = 20). The rats were allowed to survive for 3 hours, 24 hours, 3 days, or 7 days after trauma, and brains were dissected into cortical and subcortical regions ipsilateral and contralateral to injury. Additional animals were perfused and fixed for the immunocytochemical visualization of myeloperoxidase (n = 15). In the second series of experiments, rats (n = 25) were killed 3 hours or 3 days after the 3-hour monitoring period of normothermia (36.5°C), hypothermia (30°C), or hyperthemia (39°C) (n = 4 to 5 per group), and myeloperoxidase activity was again quantitated. In normothermic rats, the enzymatic activity of myeloperoxidase was significantly increased ( P < 0.05) at 3 hours within the anterior cortical segment (213.97 ± 56.2 versus control 65.5 ± 52.3 U/g of wet tissue; mean ± SD) and posterior (injured) cortical and subcortical segments compared to shamoperated rats (305.76 ± 27.8 and 258.67 ± 101.4 U/g of wet tissue versus control 62.8 ± 24.8 and 37.28 ± 35.6 U/g of wet tissue; P < 0.0001, P < 0.05, respectively). At 24 hours and 7-days after trauma only the posterior cortical region ( P < 0.005, P < 0.05, respectively) exhibited increased myeloperoxidase activity. However, 3 days after trauma, myeloperoxidase activity was also significantly increased within the anterior cortical segment ( P < 0.05) and in posterior cortical and subcortical regions compared to sham-operated cortex ( P < 0.0001, P < 0.05, respectively). Immunocytochemical analysis of myeloperoxidase reactivity at 3 hours, 24 hours, 3- and 7-days demonstrated large numbers of immunoreactive leukocytes within and associated with blood vessels, damaged tissues, and subarachnoid spaces. Posttraumatic hypothermia and hyperthermia had significant effects on myeloperoxidase activity at both 3 hours and 3 days after traumatic brain injury. Posttraumatic hypothermia reduced myeloperoxidase activity in the injured and noninjured cortical and subcortical segments compared to normothermic values ( P < 0.05). In contrast, posttraumatic hyperthermia significantly elevated myeloperoxidase activity in the posterior cortical region compared to normothermic values at both 3 hours and 3 days (473.5 ± 258.4 and 100.11 ± 27.58 U/g of wet tissue, respectively, P < 0.05 versus controls). These results indicate that posttraumatic hypothermia decreases early and more prolonged myeloperoxidase activation whereas hyperthermia increases myeloperoxidase activity. Temperature-dependent alterations in PMNL accumulation appear to be a potential mechanism by which posttraumatic temperature manipulations may influence traumatic outcome.

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