Normobaric Oxygen Worsens Outcome after a Moderate Traumatic Brain Injury

Traumatic brain injury (TBI) is a multifaceted injury and a leading cause of death in children, young adults, and increasingly in Veterans. However, there are no neuroprotective agents clinically available to counteract damage or promote repair after brain trauma. This study investigated the neuroprotective effects of normobaric oxygen (NBO) after a controlled cortical impact in rats. The central hypothesis was that NBO treatment would reduce lesion volume and functional deficits compared with air-treated animals after TBI by increasing brain oxygenation thereby minimizing ischemic injury. In a randomized double-blinded design, animals received either NBO ( n = 8) or normal air ( n = 8) after TBI. Magnetic resonance imaging (MRI) was performed 0 to 3 hours, and 1, 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. Behavioral assessments were performed before injury induction and before MRI scans on days 2, 7, and 14. Nissl staining was performed on day 14 to corroborate the lesion volume detected from MRI. Contrary to our hypothesis, we found that NBO treatment increased lesion volume in a rat model of moderate TBI and had no positive effect on behavioral measures. Our results do not promote the acute use of NBO in patients with moderate TBI.

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Neuroprotective effects of crude extract of Crataegus songarica on a rat model of traumatic brain injury

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v20i2.11 ◽

2022 ◽

Vol 20 (2) ◽

pp. 293-299

Author(s):

Xueliang Gao ◽

Zhao Wang ◽

Peilei Jia ◽

Yapeng Zhao ◽

Kai Wang ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Rat Model ◽

Brain Cortex ◽

Neuronal Survival ◽

Underlying Mechanism ◽

Tunel Staining ◽

Heme Oxygenase 1 ◽

Nissl Staining ◽

Neuroprotective Effects

Purpose: To investigate the protective effect of Crataegus songarica extract (CSCE) against traumatic brain injury (TBI) in rats, and the underlying mechanism of action. Methods: A rat model of TBI was established via tracheal intubation procedure, and the rats were treated with graded doses of CSCE. Neuronal survival was determined by Nissl staining, while neuronal apoptosis was measured using TUNEL-staining. Neurological impairments were determined based on neurological severity score (NSS). Results: Treatment of TBI rats with CSCE enhanced neuronal survival and decreased TUNEL-positive cell fraction in the brain cortex. The treatment prevented elevation of NSS and suppressed mRNA and protein expression levels of IL-6 and TNF-α in brain cortex. Moreover, CSCE treatment prevented TBI-mediated suppression of activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and attenuated hydrogen peroxide (H2O2) levels in TBI rat brain cortex. Treatment of TBI rats with CSCE down-regulated NF-κB expression, increased Nrf2 expression and up-regulated mRNA expressions of heme oxygenase 1 (HO-1) and quinine oxidoreductase 1 (NQO-1). Conclusion: These results suggest that CSCE prevents TBI-mediated reduction in neuronal survival and inhibits brain cortical neuronal death in rats. It improves NSS and inhibits inflammatory response via activation of Nrf2 pathway and targeting of NF-κB expression. Therefore, CSCE is a potential therapeutic agent for TBI.

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Propofol effects in rodent models of traumatic brain injury: a systematic review

Asian Biomedicine ◽

10.2478/abm-2021-0032 ◽

2021 ◽

Vol 15 (6) ◽

pp. 253-265

Author(s):

Riyadh Firdaus ◽

Sandy Theresia ◽

Ryan Austin ◽

Rani Tiara

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neuroprotective Effect ◽

Head Injuries ◽

Inflammatory Factors ◽

Lesion Volume ◽

Rodent Models ◽

Neuroprotective Effects ◽

Traumatic Lesion ◽

Neurotoxic Effects

Abstract Background Traumatic brain injury (TBI) causes high mortality and disability worldwide. Animal models have been developed to explore the complex processes in TBI. Propofol is used to manage head injuries during surgical intervention and mechanical ventilation in patients with TBI. Many studies have investigated the neuroprotective effect of propofol on TBI. However, other studies have shown neurotoxic effects. Objectives To review systematically the literature regarding the neuroprotective and neurotoxic effects of propofol in rodent models of TBI. Methods Data from rodents as models of TBI with propofol as one of the intervention agents, and/or comparing the neuroprotective effects of propofol with the other substances in rodent models of TBI, were obtained from PubMed, EBSCO Host, and ProQuest databases. The PRISMA 2020 statement recommendations were followed and research questions were developed based on PICOS guidelines. Data was extracted from the literature using a standardized Cochrane method. Results We analyzed data from 12 articles on physiological changes of experimental animals before and after trauma, the effects of propofol administration, and the observed neurotoxic effects. The effects of propofol administration were observed in terms of changes in traumatic lesion volume, the release of antioxidants and inflammatory factors, and the neurological function of rodent models of TBI. Conclusion Propofol has neuroprotective and neurotoxic effects via several mechanisms, and various doses have been used in research to determine its effects. The timing of administration, the dose administered, and the duration of administration contribute to determine the effect of propofol in rodent models of TBI. However, the doses that produce neuroprotective and neurotoxic effects are not yet clear and further research is needed to determine them.

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N-arachidonoyl-L-serine (AraS) Possesses Proneurogenic Properties in Vitro and in Vivo after Traumatic Brain Injury

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2013.75 ◽

2013 ◽

Vol 33 (8) ◽

pp. 1242-1250 ◽

Cited By ~ 31

Author(s):

Ayelet Cohen-Yeshurun ◽

Dafna Willner ◽

Victoria Trembovler ◽

Alexander Alexandrovich ◽

Raphael Mechoulam ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Cannabinoid Receptor ◽

Fold Increase ◽

Lesion Volume ◽

Post Injury ◽

Neuroprotective Effects ◽

Neurobehavioral Function

N-arachidonoyl-L-serine (AraS) is a novel neuroprotective endocannabinoid. We aimed to test the effects of exogenous AraS on neurogenesis after traumatic brain injury (TBI). The effects of AraS on neural progenitor cells (NPC) proliferation, survival, and differentiation were examined in vitro. Next, mice underwent TBI and were treated with AraS or vehicle. Lesion volumes and clinical outcome were evaluated and the effects on neurogenesis were tested using immunohistochemistry. Treatment with AraS led to a dose-dependent increase in neurosphere size without affecting cell survival. These effects were partially reversed by CB1, CB2, or TRPV1 antagonists. AraS significantly reduced the differentiation of NPC in vitro to astrocytes or neurons and led to a 2.5-fold increase in expression of the NPC marker nestin. Similar effects were observed in vivo in mice treated with AraS 7 days after TBI. These effects were accompanied by a reduction in lesion volume and an improvement in neurobehavioral function compared with controls. AraS increases proliferation of NPCs in vitro in cannabinoid-receptor-mediated mechanisms and maintains NPC in an undifferentiated state in vitro and in vivo. Moreover, although given at 7 days post injury, these effects are associated with significant neuroprotective effects leading to an improvement in neurobehavioral functions.

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Intranasal insulin treatment of an experimental model of moderate traumatic brain injury

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16685106 ◽

2017 ◽

Vol 37 (9) ◽

pp. 3203-3218 ◽

Cited By ~ 28

Author(s):

Fiona Brabazon ◽

Colin M Wilson ◽

Shalini Jaiswal ◽

John Reed ◽

William H Frey ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Glucose Uptake ◽

Male Rats ◽

Lesion Volume ◽

Intranasal Insulin ◽

Post Injury ◽

Fdg Uptake ◽

Moderate Traumatic Brain Injury ◽

18F Fdg

Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.

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Faculty Opinions recommendation of Neuroprotective effects of geranylgeranylacetone in experimental traumatic brain injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718074955.793482865 ◽

2013 ◽

Author(s):

Michael Tytell ◽

Mac Robinson

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neuroprotective Effects ◽

Experimental Traumatic Brain Injury

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3,6′-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury

International Journal of Molecular Sciences ◽

10.3390/ijms22158276 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8276

Author(s):

Pen-Sen Huang ◽

Ping-Yen Tsai ◽

Ling-Yu Yang ◽

Daniela Lecca ◽

Weiming Luo ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Short Term Memory ◽

Post Injury ◽

Behavioral Deficits ◽

Cognitive Behaviors ◽

Moderate Traumatic Brain Injury ◽

Short And Long Term ◽

Behavioral Impairments ◽

Hippocampal Neurodegeneration

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6′-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.

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The impact of major depression on outcome following mild-to-moderate traumatic brain injury in older adults

Yearbook of Psychiatry and Applied Mental Health ◽

10.1016/s0084-3970(08)70567-x ◽

2007 ◽

Vol 2007 ◽

pp. 267-268

Author(s):

J.C. Ballenger

Keyword(s):

Older Adults ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Major Depression ◽

Moderate Traumatic Brain Injury ◽

The Impact

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Inhaled Nitric Oxide Reduces Secondary Brain Damage after Traumatic Brain Injury in Mice

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2012.176 ◽

2012 ◽

Vol 33 (2) ◽

pp. 311-318 ◽

Cited By ~ 49

Author(s):

Nicole A Terpolilli ◽

Seong-Woong Kim ◽

Serge C Thal ◽

Wolfgang M Kuebler ◽

Nikolaus Plesnila

Keyword(s):

Nitric Oxide ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Brain Damage ◽

Brain Regions ◽

Lesion Volume ◽

Effective Treatment Option ◽

Secondary Brain Damage ◽

Edema Formation ◽

Regional Ischemia

Ischemia, especially pericontusional ischemia, is one of the leading causes of secondary brain damage after traumatic brain injury (TBI). So far efforts to improve cerebral blood flow (CBF) after TBI were not successful because of various reasons. We previously showed that nitric oxide (NO) applied by inhalation after experimental ischemic stroke is transported to the brain and induces vasodilatation in hypoxic brain regions, thus improving regional ischemia, thereby improving brain damage and neurological outcome. As regional ischemia in the traumatic penumbra is a key mechanism determining secondary posttraumatic brain damage, the aim of the current study was to evaluate the effect of NO inhalation after experimental TBI. NO inhalation significantly improved CBF and reduced intracranial pressure after TBI in male C57 Bl/6 mice. Long-term application (24 hours NO inhalation) resulted in reduced lesion volume, reduced brain edema formation and less blood–brain barrier disruption, as well as improved neurological function. No adverse effects, e.g., on cerebral auto-regulation, systemic blood pressure, or oxidative damage were observed. NO inhalation might therefore be a safe and effective treatment option for TBI patients.

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