Traumatic Brain Injury: Mechanistic Insight on Pathophysiology and Potential Therapeutic Targets

Thapa, Komal; Khan, Heena; Singh, Thakur Gurjeet; Kaur, Amandeep

doi:10.1007/s12031-021-01841-7

Cited by 143 publications

(89 citation statements)

References 165 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, no established medical therapies that promote effective therapeutic efficacy have been made, especially for the chronic phase. Therefore, a novel therapy that promotes recovery from brain damage after a chronic brain injury should be developed [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial

et al. 2022

View full text Add to dashboard Cite

Background Brain injuries resulting from motor vehicle accidents and falls, as well as hypoxic insults and other conditions, are one of the leading causes of disability and death in the world. Current treatments are limited but include continuous rehabilitation, especially for chronic brain injury. Recent studies have demonstrated that the intravenous infusion of mesenchymal stem cells (MSCs) has therapeutic efficacy for several neurological diseases, including stroke and spinal cord injury. Objective The objective of our investigator-initiated clinical trial is to assess the safety and potential efficacy of the intravenous infusion of autoserum-expanded autologous MSCs for patients with chronic brain injury. Methods The (phase 2) trial will be a single-arm, open-label trial with the primary objective of confirming the safety and efficacy of autoserum-expanded autologous MSCs (STR-01; produced under good manufacturing practices) when administered to patients with chronic brain injury. The estimated number of enrolled participants is 6 to 20 patients with a modified Rankin Scale grade of 3 to 5. The assessment of safety and the proportion of cases in which the modified Rankin Scale grade improves by 1 point or more at 180 days after the injection of STR-01 will be performed after MSC infusion. Results We received approval for our clinical trial from the Japanese Pharmaceuticals and Medical Devices Agency on December 12, 2017. The trial will be completed on June 11, 2023. The registration term is 5 years. The recruitment of the patients for this trial started on April 20, 2018, at Sapporo Medical University Hospital in Japan. Conclusions Our phase 2 study will aim to address the safety and efficacy of the intravenous infusion of MSCs for patients with chronic brain injury. The use of STR-01 has been performed for patients with cerebral infarction and spinal cord injury, providing encouraging results. The potential therapeutic efficacy of the systemic administration of autoserum-expanded autologous MSCs for chronic brain injury should be evaluated, given its safety and promising results for stroke and spinal cord injury. Trial Registration Japan Medical Association Center for Clinical Trials JMA-IIA00333; https://tinyurl.com/nzkdfnbc International Registered Report Identifier (IRRID) DERR1-10.2196/37898

show abstract

Section: Discussionmentioning

confidence: 99%

Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Sirtuin 2 protects against traumatic brain injury (TBI) by regulating chemokines. Studies have found that secondary injury occurs after TBI, resulting in chronic and progressive neurodegenerative changes ( Thapa et al, 2021 ). These mechanisms are strongly related to microglial-mediated neuroinflammation ( Aires et al, 2021 ).…”

Section: Inflammatory Factors With Neuroinflammationmentioning

confidence: 99%

Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders?

Zhang

2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Neuroinflammatory disorder is a general term that is associated with the progressive loss of neuronal structure or function. At present, the widely studied diseases with neuroinflammatory components are mainly divided into neurodegenerative and neuropsychiatric diseases, namely, Alzheimer’s disease, Parkinson’s disease, depression, stroke, and so on. An appropriate neuroinflammatory response can promote brain homeostasis, while excessive neuroinflammation can inhibit neuronal regeneration and damage the central nervous system. Apart from the symptomatic treatment with cholinesterase inhibitors, antidepressants/anxiolytics, and neuroprotective drugs, the treatment of neuroinflammation is a promising therapeutic method. Sirtuins are a host of class III histone deacetylases, that require nicotinamide adenine dinucleotide for their lysine residue deacetylase activity. The role of sirtuin 2 (SIRT2), one of the sirtuins, in modulating senescence, myelin formation, autophagy, and inflammation has been widely studied. SIRT2 is associated with many neuroinflammatory disorders considering it has deacetylation properties, that regulate the entire immune homeostasis. The aim of this review was to summarize the latest progress in regulating the effects of SIRT2 on immune homeostasis in neuroinflammatory disorders. The overall structure and catalytic properties of SIRT2, the selective inhibitors of SIRT2, the relationship between immune homeostasis and SIRT2, and the multitasking role of SIRT2 in several diseases with neuroinflammatory components were discussed.

show abstract

“…The outcome of TBI is primarily determined by two phases of pathophysiological mechanisms: primary and secondary injury. Primary injury refers to the mechanical injury of brain tissue caused by external violence immediately after injury; secondary injury refers to nerve cell dysfunction, apoptosis, and necrosis caused by inflammation, oxidative stress, disruption of the blood–brain barrier (BBB), and compression of hematoma/edema [ 2 ]. The primary injury is considered irreversible; however, secondary injury can be interfered and is therefore attractive for improving outcomes.…”

Section: Introductionmentioning

confidence: 99%

Transient post-operative overexpression of CXCR2 on monocytes of traumatic brain injury patients drives monocyte chemotaxis toward cerebrospinal fluid and enhances monocyte-mediated immunogenic cell death of neurons in vitro

Wang

Huang

Zhang

et al. 2022

J Neuroinflammation

View full text Add to dashboard Cite

Background After traumatic brain injury (TBI), peripheral monocytes infiltrate into the central nervous system due to disruption of the blood–brain barrier, and play an important role in neuroinflammation. However, the mechanisms regulating the movement and function of peripheral monocytes after TBI have not been fully investigated. Methods TBI patients who underwent surgery at our hospital were recruited. CXCR2 expression in CD14+ monocytes from peripheral blood and cerebrospinal fluid (CSF) of TBI patients around surgery was analyzed by flow cytometry and compared with that of patients who suffered TBI 2–24 months prior and underwent cranioplasty. In vitro, serum or CSF from TBI/non-TBI patients were used to treat peripheral monocytes isolated from healthy volunteers to evaluate their effect on CXCR2 expression. Transwell experiments were performed to analyze the role of CXCR2 in monocyte chemotaxis toward the CSF. The role of CXCR2 in monocyte-mediated immunogenic cell death (ICD) of nerve cells was explored in an indirect co-culture system. Results Transient CXCR2 upregulation in monocytes from the peripheral blood and CSF of TBI patients was detected soon after surgery and was associated with unfavorable outcomes. TBI serum and CSF promoted CXCR2 expression in monocytes, and dexamethasone reversed this effect. Peripheral monocytes from TBI patients showed enhanced chemotaxis toward the CSF and increased inflammatory cytokine secretion. The CXCR2 antagonist SB225002 decreased monocyte chemotaxis toward TBI CSF, and lowered pro-inflammatory cytokine secretion in monocytes treated with TBI serum. SB225002 also relieved ICD in nerve cells co-cultured with TBI serum-treated monocytes. Conclusions CXCR2 is transiently overexpressed in the peripheral monocytes of TBI patients post-surgery, and drives peripheral monocyte chemotaxis toward CSF and monocyte-mediated ICD of nerve cells. Therefore, CXCR2 may be a target for monocyte-based therapies for TBI.

show abstract

Traumatic Brain Injury: Mechanistic Insight on Pathophysiology and Potential Therapeutic Targets

Cited by 143 publications

References 165 publications

Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial

Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial

Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders?

Transient post-operative overexpression of CXCR2 on monocytes of traumatic brain injury patients drives monocyte chemotaxis toward cerebrospinal fluid and enhances monocyte-mediated immunogenic cell death of neurons in vitro

Contact Info

Product

Resources

About