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

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.

scholarly journals Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Rita Campos-Pires ◽  
Haldis Onggradito ◽  
Eszter Ujvari ◽  
Shughoofa Karimi ◽  
Flavia Valeo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Functional Outcome ◽  
Neuroprotective Effect ◽  
Neuronal Loss ◽  
Brain Trauma ◽  
Lesion Volume ◽  
Oxygen Balance ◽  
Sprague Dawley ◽  
Locomotor Deficits

Abstract Background Traumatic brain injury (TBI) is a major cause of morbidity and mortality, but there are no clinically proven treatments that specifically target neuronal loss and secondary injury development following TBI. In this study, we evaluate the effect of xenon treatment on functional outcome, lesion volume, neuronal loss and neuroinflammation after severe TBI in rats. Methods Young adult male Sprague Dawley rats were subjected to controlled cortical impact (CCI) brain trauma or sham surgery followed by treatment with either 50% xenon:25% oxygen balance nitrogen, or control gas 75% nitrogen:25% oxygen. Locomotor function was assessed using Catwalk-XT automated gait analysis at baseline and 24 h after injury. Histological outcomes were assessed following perfusion fixation at 15 min or 24 h after injury or sham procedure. Results Xenon treatment reduced lesion volume, reduced early locomotor deficits, and attenuated neuronal loss in clinically relevant cortical and subcortical areas. Xenon treatment resulted in significant increases in Iba1-positive microglia and GFAP-positive reactive astrocytes that was associated with neuronal preservation. Conclusions Our findings demonstrate that xenon improves functional outcome and reduces neuronal loss after brain trauma in rats. Neuronal preservation was associated with a xenon-induced enhancement of microglial cell numbers and astrocyte activation, consistent with a role for early beneficial neuroinflammation in xenon’s neuroprotective effect. These findings suggest that xenon may be a first-line clinical treatment for brain trauma.

scholarly journals Reduction of Traumatic Brain Damage by Tspo Ligand Etifoxine

2019 ◽  
Vol 20 (11) ◽  
pp. 2639 ◽  
Author(s):  
Mona Shehadeh ◽  
Eilam Palzur ◽  
Liat Apel ◽  
Jean Francois Soustiel
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Experimental Studies ◽  
Potential Effect ◽  
Translocator Protein ◽  
Male Rats ◽  
Lesion Volume ◽  
Sprague Dawley

Experimental studies have shown that ligands of the 18 kDa translocator protein can reduce neuronal damage induced by traumatic brain injury by protecting mitochondria and preventing metabolic crisis. Etifoxine, an anxiolytic drug and 18 kDa translocator protein ligand, has shown beneficial effects in the models of peripheral nerve neuropathy. The present study investigates the potential effect of etifoxine as a neuroprotective agent in traumatic brain injury (TBI). For this purpose, the effect of etifoxine on lesion volume and modified neurological severity score at 4 weeks was tested in Sprague–Dawley adult male rats submitted to cortical impact contusion. Effects of etifoxine treatment on neuronal survival and apoptosis were also assessed by immune stains in the perilesional area. Etifoxine induced a significant reduction in the lesion volume compared to nontreated animals in a dose-dependent fashion with a similar effect on neurological outcome at four weeks that correlated with enhanced neuron survival and reduced apoptotic activity. These results are consistent with the neuroprotective effect of etifoxine in TBI that may justify further translational research.

scholarly journals Neuroprotective Effects of Tempol, a Catalytic Scavenger of Peroxynitrite-Derived Free Radicals, in a Mouse Traumatic Brain Injury Model

2008 ◽  
Vol 28 (6) ◽  
pp. 1114-1126 ◽  
Author(s):  
Ying Deng-Bryant ◽  
Indrapal N Singh ◽  
Kimberly M Carrico ◽  
Edward D Hall
Keyword(s):  
Traumatic Brain Injury ◽  
Free Radicals ◽  
Brain Injury ◽  
Oxidative Damage ◽  
Mitochondrial Dysfunction ◽  
Neuroprotective Effect ◽  
Complete Suppression ◽  
Post Injury ◽  
Multiple Dosing ◽  
Neuroprotective Effects

We examined the ability of tempol, a catalytic scavenger of peroxynitrite (PN)-derived free radicals, to reduce cortical oxidative damage, mitochondrial dysfunction, calpain-mediated cytoskeletal (α-spectrin) degradation, and neurodegeneration, and to improve behavioral recovery after a severe (depth 1.0 mm), unilateral controlled cortical impact traumatic brain injury (CCI-TBI) in male CF-1 mice. Administration of a single 300 mg/kg intraperitoneal dose of tempol 15 mins after TBI produced a complete suppression of PN-mediated oxidative damage (3-nitrotyrosine, 3NT) in injured cortical tissue at 1 h after injury. Identical tempol dosing maintained respiratory function and attenuated 3NT in isolated cortical mitochondria at 12 h after injury, the peak of mitochondrial dysfunction. Multiple dosing with tempol (300 mg/kg intraperitoneally at 15 mins, 3, 6, 9, and 12 h) also suppressed α-spectrin degradation by 45% at its 24 h post-injury peak. The same dosing regimen improved 48 h motor function and produced a significant, but limited (17.4%, P<0.05), decrease in hemispheric neurodegeneration at 7 days. These results are consistent with a mechanistic link between PN-mediated oxidative damage to brain mitochondria, calpain-mediated proteolytic damage, and neurodegeneration. However, the modest neuroprotective effect of tempol suggests that multitarget combination strategies may be needed to interfere with posttraumatic secondary injury to a degree worthy of clinical translation.

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

2013 ◽  
Vol 33 (8) ◽  
pp. 1242-1250 ◽  
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.

scholarly journals The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chung-Che Lu ◽  
Tee-Tau Eric Nyam ◽  
Jinn-Rung Kuo ◽  
Yao-Lin Lee ◽  
Chung-Ching Chio ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glutamate Receptor ◽  
Neuronal Apoptosis ◽  
Nitrosative Stress ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Motor Deficits ◽  
Sprague Dawley ◽  
Neuroprotective Effects

Abstract Background The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). Methods Anesthetized male Sprague–Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-d-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI. Results The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells. Conclusions We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.

scholarly journals Normobaric Oxygen Worsens Outcome after a Moderate Traumatic Brain Injury

2015 ◽  
Vol 35 (7) ◽  
pp. 1137-1144 ◽  
Author(s):  
Lora Talley Watts ◽  
Justin Alexander Long ◽  
Venkata Hemanth Manga ◽  
Shiliang Huang ◽  
Qiang Shen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Lesion Volume ◽  
Nissl Staining ◽  
Neuroprotective Effects ◽  
Normobaric Oxygen ◽  
Moderate Traumatic Brain Injury ◽  
Mri Scans ◽  
Behavioral Assessments ◽  
Double Blinded

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.

Abstract W P201: Angiopoietin-1 Mimetic Peptide Treatment of Stroke Regulates MicroRNA Expression and Promotes Neuroprotection in Type One Diabetic Rats

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Alex Zacharek ◽  
Michael Chopp ◽  
Ruizhuo Ning ◽  
Tao Yan ◽  
Paul Van Slyke ◽  
...  
Keyword(s):  
Western Blot ◽  
Mirna Expression ◽  
Neuroprotective Effect ◽  
Diabetic Rats ◽  
Inflammatory Factors ◽  
Lesion Volume ◽  
Brain Hemorrhage ◽  
Neuroprotective Effects ◽  
Mimetic Peptide ◽  
Angiopoietin 1

Introduction: Angiopoietin-1 (Ang-1) mediates vascular remodeling. Diabetes decreases Ang1 and disrupts Ang1/Tie2 signaling, impairs vascular maturation and regulates immune response. MicroRNAs have been implicated in vascular diseases and inflammation. Vasculotide (VT) is an Ang1 mimetic peptide that promotes Tie2 activity. We hypothesize that treating type one diabetic rats (T1DM) with VT after stroke regulates miRNA expression decreases pro-inflammatory factors and thereby produces a neuroprotective effect. Methods: T1DM was induced in male Wistar rats with streptozotocin followed by 2h transient middle cerebral artery occlusion (MCAo). These rats were then treated with: 1) PBS control; 2) VT (3 ug/kg, ip injection) just prior to stroke and at 8h and 24h after MCAo. Functional tests were conducted 48h after MCAo. Afterwards, brain hemorrhage, BBB leakage, miRNA expression, RT-PCR, immunostaining and Western blot assays were done. Results: VT treatment did not decrease brain hemorrhage, but significantly decreased Evans Blue leakage (30.6±5.8 ng/mg vs. 17.9±2.0 ng/mg) lesion volume (35.1±3.5% vs 25.8±5.3%) and improved functional outcome after stroke when compared to control (p<0.05). To elucidate the mechanism, miRNA was measured. VT treatment significantly increased miR-451 (81.6 folds), miR-155 (2.4 fold), miR-98 (1.9 fold), and miR-126 (1.5 fold) expression, but decreased miR-200b (3.8 fold). Immunostaining showed that VT significantly decreased the number of apoptotic (45.5±3.7 vs 30.8±2.6) and cleaved-caspase-3 positive cells (45.2±3.5 vs 33.1±4.3), as well as monocyte chemotactic protein-1 (MCP1, 5.02±0.4% vs 1.8±0.2%) and tumor necrosis factor (TNF)-alpha (3.1±0.5% vs 1.5±0.2%). Western blot showed that VT significantly decreased receptor for advanced glycation end products (RAGE), MCP1 and TNFa (3-5 fold) in the ischemic border area compared to T1DM control. Conclusion: VT promotes neuroprotection after stroke in T1DM rats. Regulation of miRNA and neuroinflammatory factor expression and decreased BBB leakage may contribute to the VT induced neuroprotective effects observed after stroke in T1DM rats.

scholarly journals The neuroprotective effects of AMN082 on neuronal apoptosis in rat after traumatic brain injury

2020 ◽  
Author(s):  
Chung-Che Lu ◽  
Che-Chuan Wang ◽  
Yao-Lin Lee ◽  
Chung-Ching Chio ◽  
Sher-Wei Lim ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Apoptosis ◽  
Nitrosative Stress ◽  
Neuroprotective Effect ◽  
Acute Stage ◽  
Motor Deficits ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Infarction Volume

Abstract The aim of this study is to investigate whether the neuroprotective effect of AMN082 is via attenuating glutamic receptor associated neuronal apoptosis and improves functional outcomes after traumatic brain injury (TBI). Anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 was intraperitoneally injected (10 mg/kg) at 0, 24, and 48 hr after TBI. During the 120 minutes after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. The motor function, infarction volume, and neuronal nitrosative stress-associated apoptosis, N-Methyl-D-aspartate receptor 2A (NR2A) and NR2B expression were measured on the 3rd day after TBI. The results showed AMN082-treated group had the lower ICP and higher CPP after TBI. The TBI-induced motor deficits, increased infarction volume, neuronal apoptosis, 3-nitrotyrosine and inducible nitric oxide synthase expression in the peri-contusion cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased the NR2A and NR2B expression in neuronal cells. We concluded intraperitoneal injection of AMN082 for 3 days may ameliorate TBI insults by attenuating glutamic receptor associated nitrosative stress and neuronal apoptosis in the peri-contusion cortex. We suggest AMN082 administration in acute stage may be a promising strategy for TBI.

scholarly journals C1q/CTRP1 exerts neuroprotective effects in TBI rats by regulating inflammation and autophagy

2020 ◽  
Author(s):  
Ming Pei ◽  
Chaoqun Wang ◽  
Zhengdong Li ◽  
Jianhua Zhang ◽  
Ping Huang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
Inflammatory Factors ◽  
Vehicle Group ◽  
Secondary Brain Injury ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion Injury

AbstractObjectiveC1q/CTRP1 is a newly discovered adiponectin protein, which is highly expressed in adipose and heart tissues. Recent studies have revealed that C1q/CTRP1 can regulate metabolism and inhibit inflammation. CTRP1 is also expressed in brain tissues and vascular cells of human and rat, and research on cerebral hemorrhage and cerebral ischemia-reperfusion injury demonstrates that the CTRP family can attenuate secondary brain injury and exert neuroprotective effects. Thus, this study was designed to explore the role of CTRP1 in traumatic brain injury (TBI) and the underlying mechanism.Main methodsRats were assigned into rCTRP1 group, vehicle group, and sham group. Modified Feeney’s method was used to establish a closed traumatic brain injury model. Morris water maze was used for directional navigation, reverse searching and space exploration tests in rats. In addition, Golgi-Cox staining was utilized to visualize neurons, dendrites and dendritic spines. ELISA was conducted to detect the levels of inflammatory factors (IL-6 and TNF-α). Finally, Western blot was adopted to detect the relative expression of p-mTOR and autophagy-related proteins (Beclin-1 and LC3-II).ResultsCTRP1 improved the behavioral and histopathological outcomes, inhibited the inflammatory response, activated mTOR and decreased autophagy-associated protein synthesis in TBI rats.ConclusionCTRP1 exerts neuroprotective effects in TBI rats by regulating inflammation and autophagy and has potential therapeutic properties after TBI.

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