Structural and Functional Damage Sustained by Mitochondria after Traumatic Brain Injury in the Rat: Evidence for Differentially Sensitive Populations in the Cortex and Hippocampus

2003 ◽  
Vol 23 (2) ◽  
pp. 219-231 ◽  
Author(s):  
Jonathan Lifshitz ◽  
Hans Friberg ◽  
Robert W. Neumar ◽  
Ramesh Raghupathi ◽  
Frank A. Welsh ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Structural Integrity ◽  
Mitochondrial Permeability Transition ◽  
Mitochondrial Protein ◽  
Permeability Transition ◽  
Calcium Sensitivity ◽  
Correlation Spectroscopy ◽  
Metabolic Dysfunction ◽  
Injured Brain

The cellular and molecular pathways initiated by traumatic brain injury (TBI) may compromise the function and structural integrity of mitochondria, thereby contributing to cerebral metabolic dysfunction and cell death. The extent to which TBI affects regional mitochondrial populations with respect to structure, function, and swelling was assessed 3 hours and 24 hours after lateral fluid—percussion brain injury in the rat. Significantly less mitochondrial protein was isolated from the injured compared with uninjured parietotemporal cortex, whereas comparable yields were obtained from the hippocampus. After injury, cortical and hippocampal tissue ATP concentrations declined significantly to 60% and 40% of control, respectively, in the absence of respiratory deficits in isolated mitochondria. Mitochondria with ultrastructural morphologic damage comprised a significantly greater percent of the population isolated from injured than uninjured brain. As determined by photon correlation spectroscopy, the mean mitochondrial radius decreased significantly in injured cortical populations (361 ± 40 nm at 24 hours) and increased significantly in injured hippocampal populations (442 ± 36 at 3 hours) compared with uninjured populations (Ctx: 418 ± 44; Hipp: 393 ± 24). Calcium-induced deenergized swelling rates of isolated mitochondrial populations were significantly slower in injured compared with uninjured samples, suggesting that injury alters the kinetics of mitochondrial permeability transition (MPT) pore activation. Cyclosporin A (CsA)-insensitive swelling was reduced in the cortex, and CsA-sensitive and CsA-insensitive swelling both were reduced in the hippocampus, demonstrating that regulated MPT pores remain in mitochondria isolated from injured brain. A proposed mitochondrial population model synthesizes these data and suggests that cortical mitochondria may be depleted after TBI, with a physically smaller, MPT-regulated population remaining. Hippocampal mitochondria may sustain damage associated with ballooned membranes and reduced MPT pore calcium sensitivity. The heterogeneous mitochondrial response to TBI may underlie posttraumatic metabolic dysfunction and contribute to the pathophysiology of TBI.

scholarly journals Etifoxine Restores Mitochondrial Oxidative Phosphorylation and Improves Cognitive Recovery Following Traumatic Brain Injury

2021 ◽  
Vol 22 (23) ◽  
pp. 12881
Author(s):  
Eilam Palzur ◽  
Doron Edelman ◽  
Reem Sakas ◽  
Jean Francois Soustiel
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Oxidative Phosphorylation ◽  
Cognitive Functions ◽  
Mitochondrial Permeability Transition ◽  
Neuroprotective Effect ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Translocator Protein ◽  
The Impact

The opening of the mitochondrial permeability transition pore (mPTP) has emerged as a pivotal event following traumatic brain injury (TBI). Evidence showing the impact of the translocator protein (TSPO) over mPTP activity has prompted several studies exploring the effect of TSPO ligands, including etifoxine, on the outcome of traumatic brain injury (TBI). Mitochondrial respiration was assessed by respirometry in isolated rat brain mitochondria (RBM) by measurements of oxidative phosphorylation capacity (OXPHOS). The addition of calcium to RBM was used to induce mitochondrial injury and resulted in significant OXPHOS reduction that could be reversed by preincubation of RBM with etifoxine. Sensorimotor and cognitive functions were assessed following controlled cortical impact and compared in vehicle and etifoxine-treated animals. There was no difference between the vehicle and etifoxine groups for sensorimotor functions as assessed by rotarod. In contrast, etifoxine resulted in a significant improvement of cognitive functions expressed by faster recovery in Morris water maze testing. The present findings show a significant neuroprotective effect of etifoxine in TBI through restoration of oxidative phosphorylation capacity associated with improved behavioral and cognitive outcomes. Since etifoxine is a registered drug used in common clinical practice, implementation in a phase II study may represent a reasonable step forward.

Traumatic Brain Injury: A Trauma Surgeon's Perspective

2012 ◽  
Vol 22 (3) ◽  
pp. 82-89
Author(s):  
Oscar D. Guillamondegui
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Multidisciplinary Approach ◽  
Trauma Team ◽  
The United States ◽  
Long Term Outcomes ◽  
Term Care ◽  
Injured Brain ◽  
The Moment

Traumatic brain injury (TBI) is a serious epidemic in the United States. It affects patients of all ages, race, and socioeconomic status (SES). The current care of these patients typically manifests after sequelae have been identified after discharge from the hospital, long after the inciting event. The purpose of this article is to introduce the concept of identification and management of the TBI patient from the moment of injury through long-term care as a multidisciplinary approach. By promoting an awareness of the issues that develop around the acutely injured brain and linking them to long-term outcomes, the trauma team can initiate care early to alter the effect on the patient, family, and community. Hopefully, by describing the care afforded at a trauma center and by a multidisciplinary team, we can bring a better understanding to the armamentarium of methods utilized to treat the difficult population of TBI patients.

scholarly journals Limited Fronto-Temporo- Parietal Craniectomy in Traumatic Brain Injury: My Experience

2016 ◽  
Vol 12 (1) ◽  
pp. 8-13
Author(s):  
Krishna Sharma
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Single Step ◽  
Temporalis Fascia ◽  
Related Literature ◽  
Primary Surgery ◽  
Injured Brain ◽  
Life Saving ◽  
Second Surgery ◽  
Different Types

Amidst the uncertainty of benefit of decompressive craniectomy (DC) in severe traumatic brain injury (TBI), the procedure is still widely performed as a life saving attempt. Different types of DC have been described. A timely performed limited fronto-temporoparietal (FTP) decompression is found to be adequate enough to reduce the intracranial pressure (ICP) quickly and sufficiently, preventing medial temporal herniation. This can be further augmented by an adequate, liberal and watertight duroplasty to accommodate the swollen injured brain, which can be achieved by using patients’ own tissues like thickened subcutaneous areolar tissue and temporalis fascia. DC is usually considered as a two-step surgery where decompression is done in the first step and cranioplasty in the second. It can be made a single step surgery by replacing the bone in small pieces extradurally during the primary surgery itself, to avoid second surgery (cranioplasty). The details of the procedure and its results have been described and review of related literature has been done.Nepal Journal of Neuroscience 12:8-13, 2015

scholarly journals The Roles of Neurotrophins in Traumatic Brain Injury

Life ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 26
Author(s):  
Ping-Hung Lin ◽  
Lu-Ting Kuo ◽  
Hui-Tzung Luh
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neural Development ◽  
Tissue Destruction ◽  
Compensatory Mechanisms ◽  
Injured Brain ◽  
Severity Of Injury ◽  
Brain Barrier Permeability ◽  
Post Traumatic ◽  
Related Proteins

Neurotrophins are a collection of structurally and functionally related proteins. They play important roles in many aspects of neural development, survival, and plasticity. Traumatic brain injury (TBI) leads to different levels of central nervous tissue destruction and cellular repair through various compensatory mechanisms promoted by the injured brain. Many studies have shown that neurotrophins are key modulators of neuroinflammation, apoptosis, blood–brain barrier permeability, memory capacity, and neurite regeneration. The expression of neurotrophins following TBI is affected by the severity of injury, genetic polymorphism, and different post-traumatic time points. Emerging research is focused on the potential therapeutic applications of neurotrophins in managing TBI. We conducted a comprehensive review by organizing the studies that demonstrate the role of neurotrophins in the management of TBI.

Multimodality Monitoring

2018 ◽  
pp. 155-164
Author(s):  
Maranatha Ayodele ◽  
Kristine O’Phelan
Keyword(s):  
Traumatic Brain Injury ◽  
Critical Care ◽  
Brain Injury ◽  
Early Recognition ◽  
Secondary Injury ◽  
Multimodality Monitoring ◽  
Injured Brain ◽  
Brain Injured ◽  
Physiologic Parameters ◽  
Injured Patients

Advancements in the critical care of patients with various forms of acute brain injury (traumatic brain injury, subarachnoid hemorrhage, stroke, etc.) in its current evolution recognizes that in addition to the initial insult, there is a secondary cascade of physiological events in the injured brain that contribute significantly to morbidity and mortality. Multimodality monitoring (MMM) in neurocritical care aims to recognize this secondary cascade in a timely manner. With early recognition, critical care of brain-injured patients may then be tailored to preventing and alleviating this secondary injury. MMM includes a variety of invasive and noninvasive techniques aimed at monitoring brain physiologic parameters such as intracranial pressure, perfusion, oxygenation, blood flow, metabolism, and electrical activity. This chapter provides an overview of these techniques and offers a practical guide to their integration and use in the intensive care setting.

scholarly journals Role of Thalamus in Recovery of Traumatic Brain Injury

2016 ◽  
Vol 07 (S 01) ◽  
pp. S076-S079 ◽  
Author(s):  
Ashok Munivenkatappa ◽  
Amit Agrawal
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Structures ◽  
Thalamic Nuclei ◽  
Posttraumatic Symptoms ◽  
Injured Brain ◽  
Recovery Mechanisms ◽  
The Brain ◽  
Degree Of Recovery

ABSTRACTDegree of recovery after traumatic brain injury is highly variable that lasts for many weeks to months. The evidence of brain structures involved in recovery mechanisms is limited. This review highlights evidence of the brain structure particularly thalamus in neuroplasticity mechanism. Thalamus with its complex global networking has potential role in refining the cortical and other brain structures. Thalamic nuclei activation both naturally or by neurorehabilitation in injured brain can enhance and facilitate the improvement of posttraumatic symptoms. This review provides evidence from literature that thalamus plays a key role in recovery mechanism after injury. The study also emphasize that thalamus should be specifically targeted in neurorehabilitation following brain injury.

scholarly journals Multiple Sites of Vasopressin Synthesis in the Injured Brain

2010 ◽  
Vol 31 (1) ◽  
pp. 47-51 ◽  
Author(s):  
Joanna Szmydynger-Chodobska ◽  
Brian J Zink ◽  
Adam Chodobski
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebral Cortex ◽  
Brain Injury ◽  
Impact Model ◽  
Proinflammatory Mediators ◽  
Injured Brain ◽  
Pathophysiological Role ◽  
Cerebrovascular Endothelium ◽  
Vasopressin Synthesis

Previous studies have indicated that the primary targets for vasopressin actions on the injured brain are the cerebrovascular endothelium and astrocytes, and that vasopressin amplifies the posttraumatic production of proinflammatory mediators. Here, the controlled cortical impact model of traumatic brain injury in rats was used to identify the sources of vasopressin in the injured brain. Injury increased vasopressin synthesis in the hypothalamus and cerebral cortex adjacent to the posttraumatic lesion. In the cortex, vasopressin was predominantly produced by activated microglia/macrophages, and, to a lesser extent, by the cerebrovascular endothelium. These data further support the pathophysiological role of vasopressin in brain injury.

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