Icariin Improves Functional Behavior in a Mouse Model of Traumatic Brain Injury and Promotes Synaptic Plasticity Markers

AbstractEpimedii Herba (EH) has been used in traditional Asian medicine to treat hemiplegia following stroke. Icariin, its major active component, is used as a quality-control marker and for its various pharmacological effects. We hypothesized that icariin would show protective effects following traumatic brain injury (TBI). The TBI mouse model was induced using a controlled cortical impact method. Body weight, brain damage, motor function, and cognitive function were evaluated. Synaptogenesis markers were analyzed to investigate potential mechanisms of action. The animals were divided into six groups: sham, control, minocycline-treated group, and icariin-treated (3, 10, and 30 mg/kg, p. o.) groups. The icariin 30 mg/kg-treated group regained body weight at 7 and 8 d post TBI. Icariin 30 mg/kg- and 10 mg/kg-treated groups showed enhanced sensory-motor function at 8 d post TBI in rotarod and balance beam tests. Icariin-treated groups showed increased recognition index in the novel object recognition test at all doses and increased spontaneous alternation in the Y-maze test at 30 mg/kg. Icariin upregulated brain-derived neurotrophic factor, synaptophysin and postsynaptic density protein 95 expressions. However, no protective effects against brain damage or neuronal death were observed. The current results provide a basis for using icariin following TBI and suggest that it could be a candidate for the development of therapeutic agents for functional recovery after TBI.

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Protective Effects of N-Oleoylglycine in a Mouse Model of Mild Traumatic Brain Injury

ACS Chemical Neuroscience ◽

10.1021/acschemneuro.9b00633 ◽

2020 ◽

Vol 11 (8) ◽

pp. 1117-1128

Author(s):

Fabiana Piscitelli ◽

Francesca Guida ◽

Livio Luongo ◽

Fabio Arturo Iannotti ◽

Serena Boccella ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mouse Model ◽

Mild Traumatic Brain Injury ◽

Protective Effects

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The Effects of Chunghyul-Dan, an Agent of Korean Medicine, on a Mouse Model of Traumatic Brain Injury

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/7326107 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Won-Woo Choi ◽

Kyungjin Lee ◽

Beom-Joon Lee ◽

Seong-Uk Park ◽

Jung-Mi Park ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mouse Model ◽

Brain Edema ◽

Brain Damage ◽

Motor Deficits ◽

Pharmacological Effects ◽

Beneficial Effects ◽

First Choice ◽

Prevention And Treatment

Chunghyul-Dan (CHD) is the first choice agent for the prevention and treatment of stroke at the Kyung Hee Medical Hospital. To date, CHD has been reported to have beneficial effects on brain disease in animals and humans, along with antioxidative and anti-inflammatory effects. The aim of this study was to evaluate the pharmacological effects of CHD on a traumatic brain injury (TBI) mouse model to explore the possibility of CHD use in patients with TBI. The TBI mouse model was induced using the controlled cortical impact method. CHD was orally administered twice a day for 5 d after TBI induction; mice were assessed for brain damage, brain edema, blood-brain barrier (BBB) damage, motor deficits, and cognitive impairment. Treatment with CHD reduced brain damage seen on histological examination and improved motor and cognitive functions. However, CHD did not reduce brain edema and BBB damage. In conclusion, CHD could be a candidate agent in the treatment of patients with TBI. Further studies are needed to assess the exact mechanisms of the effects during the acute-subacute phase and pharmacological activity during the chronic-convalescent phase of TBI.

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FGF20 Protected Against BBB Disruption After Traumatic Brain Injury by Upregulating Junction Protein Expression and Inhibiting the Inflammatory Response

Frontiers in Pharmacology ◽

10.3389/fphar.2020.590669 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jun Chen ◽

Xue Wang ◽

Jian Hu ◽

Jingting Du ◽

Confidence Dordoe ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Inflammatory Response ◽

Mouse Model ◽

Protein Expression ◽

Microvascular Endothelial Cell ◽

Potential Candidate ◽

Protective Effects ◽

Junction Protein

Disruption of the blood-brain barrier (BBB) and the cerebral inflammatory response occurring after traumatic brain injury (TBI) facilitate further brain damage, which leads to long-term complications of TBI. Fibroblast growth factor 20 (FGF20), a neurotrophic factor, plays important roles in brain development and neuronal homeostasis. The aim of the current study was to assess the protective effects of FGF20 on TBI via BBB maintenance. In the present study, recombinant human FGF20 (rhFGF20) reduced neurofunctional deficits, brain edema, Evans blue extravasation and neuroinflammation in a TBI mouse model. In an in vitro TNF-α-induced human brain microvascular endothelial cell (HBMEC) model of BBB disruption, rhFGF20 reduced paracellular permeability and increased trans-endothelial electrical resistance (TEER). Both in the TBI mouse model and in vitro, rhFGF20 increased the expression of proteins composing in BBB-associated tight junctions (TJs) and adherens junctions (AJs), and decreased the inflammatory response, which protected the BBB integrity. Notably, rhFGF20 preserved BBB function by activating the AKT/GSK3β pathway and inhibited the inflammatory response by regulating the JNK/NFκB pathway. Thus, FGF20 is a potential candidate treatment for TBI that protects the BBB by upregulating junction protein expression and inhibiting the inflammatory response.

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Protective Effects of Aquaporin-4 Deficiency on Longer-Term Neurological Outcomes in a Mouse Model of Traumatic Brain Injury

10.21203/rs.3.rs-104428/v1 ◽

2020 ◽

Author(s):

Xiaosong Liu ◽

Yingxin Xie ◽

Xiangdong Wan ◽

Jianliang Wu ◽

Zhenzeng Fan ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mouse Model ◽

Water Channel ◽

Amyloid Β ◽

Aquaporin 4 ◽

Protective Effects ◽

Fluid Exchange ◽

Glymphatic System ◽

Neurological Outcomes

Abstract Background: Traumatic brain injury (TBI) has been a crucial health problem, with more than 50 million patients worldwide each year. Glymphatic system is a fluid exchange system that relies on the polarized water channel aquaporin-4 (AQP4) at the astrocytes, accounting for the clearance of abnormal proteins and metabolites from brain tissues. However, the dysfunction of glymphatic system and alteration of AQP4 polarization during the progression of TBI remain unclear.Methods: AQP4−/− and Wild Type (WT) mice were used to establish the TBI mouse model respectively. Morris water maze (MWM) was used to establish the cognitive functions of AQP4−/− and WT mice post TBI. Western-blot and qRT-PCR assays were performed to demonstrate protective effects of AQP4 deficiency to blood-brain barrier (BBB) integrity and amyloid-β clearance. The inflammation of cerebral tissues post TBI was estimated by ELISA assay.Results: AQP4 deficiency alleviated the brain edema and neurological deficit in TBI mice. AQP4-knockout led to improved cognitive outcomes in mice post TBI. The BBB integrity and cerebral amyloid-β clearance were protected by AQP4 deficiency in TBI mice. AQP4 deficiency ameliorated the TBI-induced inflammation.Conclusion: AQP4 deficiency improved longer-term neurological outcomes in a mouse model of TBI.

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Lipoxin A4 attenuates brain damage and downregulates the production of pro-inflammatory cytokines and phosphorylated mitogen-activated protein kinases in a mouse model of traumatic brain injury

Brain Research ◽

10.1016/j.brainres.2013.01.037 ◽

2013 ◽

Vol 1502 ◽

pp. 1-10 ◽

Cited By ~ 34

Author(s):

Cheng-Liang Luo ◽

Qian-Qian Li ◽

Xi-Ping Chen ◽

Xin-Mu Zhang ◽

Li-Liang Li ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mouse Model ◽

Protein Kinases ◽

Brain Damage ◽

Inflammatory Cytokines ◽

Lipoxin A4 ◽

Mitogen Activated Protein Kinases ◽

Mitogen Activated Protein ◽

Pro Inflammatory Cytokines

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Coadministration of Ketamine and Perampanel Improves Behavioral Function and Reduces Inflammation in Acute Traumatic Brain Injury Mouse Model

BioMed Research International ◽

10.1155/2020/3193725 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Faleh Alqahtani ◽

Mohammed A. Assiri ◽

Mohamed Mohany ◽

Imran Imran ◽

Sana Javaid ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Age Groups ◽

Anxiolytic Effect ◽

Plasma Metabolites ◽

Object Recognition Test ◽

Behavioral Challenges ◽

Maze Test ◽

Y Maze ◽

The Impact

Traumatic brain injury (TBI) is among the most debilitating neurological disorders with inadequate therapeutic options. It affects all age groups globally leading to post-TBI behavioral challenges and life-long disabilities requiring interventions for these health issues. In the current study, C57BL/6J mice were induced with TBI through the weight-drop method, and outcomes of acutely administered ketamine alone and in combination with perampanel were observed. The impact of test drugs was evaluated for post-TBI behavioral changes by employing the open field test (OFT), Y-maze test, and novel object recognition test (NOR). After that, isolated plasma and brain homogenates were analyzed for inflammatory modulators, i.e., NF-κB and iNOS, through ELISA. Moreover, metabolomic studies were carried out to further authenticate the TBI rescuing potential of drugs. The animals treated with ketamine-perampanel combination demonstrated improved exploratory behavior in OFT ( P < 0.05 ), while ketamine alone as well as in combination yielded anxiolytic effect ( P < 0.05 ‐ 0.001 ) in posttraumatic mice. Similarly, the % spontaneous alternation and % discrimination index were increased after the administration of ketamine alone ( P < 0.05 ) and ketamine-perampanel combination ( P < 0.01 ‐ 0.001 ) in the Y-maze test and NOR test, respectively. ELISA demonstrated the reduced central and peripheral expression of NF-κB ( P < 0.05 ) and iNOS ( P < 0.01 ‐ 0.0001 ) after ketamine-perampanel polypharmacy. The TBI-imparted alteration in plasma metabolites was restored by drug combination as evidenced by metabolomic studies. The outcomes were fruitful with ketamine, but the combination therapy proved more significant in improving all studied parameters. The benefits of this new investigated polypharmacy might be due to their antiglutamatergic, antioxidant, and neuroprotective capacity.

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