Endogenous opioids may mediate secondary damage after experimental brain injury

1987 ◽  
Vol 253 (5) ◽  
pp. E565-E574 ◽  
Author(s):  
T. K. McIntosh ◽  
R. L. Hayes ◽  
D. S. DeWitt ◽  
V. Agura ◽  
A. I. Faden
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Traumatic Injury ◽  
Opiate Receptors ◽  
Opiate Receptor ◽  
Endogenous Opioids ◽  
Secondary Brain Injury ◽  
Secondary Damage ◽  
Cord Injury

Although endogenous opioids have been implicated in the pathophysiology of spinal cord injury and brain ischemia, the role of specific opioid peptides and opiate receptors in the pathophysiology of traumatic brain injury remains unexplored. This study examined regional changes in brain opioid immunoreactivity and cerebral blood flow (CBF) after fluid-percussion brain injury in the cat and compared the effect of an opiate antagonist (Win 44,441-3 [Win-(-)]) with its dextroisomer Win 44,441-2 [Win-(+)] (which is inactive at opiate receptors) in the treatment of brain injury. Dynorphin A immunoreactivity (Dyn A-IR) but not leucine-enkephalin-like immunoreactivity accumulated in injury regions after traumatic injury; Dyn-IR increases also occurred predominantly in those areas showing significant decreases in regional CBF. Administration of Win-(-) but not Win-(+) or saline at 15 min after injury significantly improved mean arterial pressure, electroencephalographic amplitude, and regional CBF and reduced the severity and incidence of hemorrhage. Win-(-) also significantly improved survival after brain injury. Taken together, these findings suggest that dynorphin, through actions at opiate receptors, may contribute to the pathophysiology of secondary brain injury after head trauma and indicate that selective opiate-receptor antagonists may be useful in treatment of traumatic brain injury.

The Role of Free Radicals in Traumatic Brain Injury

2012 ◽  
Vol 15 (3) ◽  
pp. 253-263 ◽  
Author(s):  
Karen M. O’Connell ◽  
Marguerite T. Littleton-Kearney
Keyword(s):  
Traumatic Brain Injury ◽  
Free Radicals ◽  
Free Radical ◽  
Brain Injury ◽  
Current Knowledge ◽  
Cellular Level ◽  
Secondary Brain Injury ◽  
Secondary Injury ◽  
The Military

Traumatic brain injury (TBI) is a significant cause of death and disability in both the civilian and the military populations. The primary impact causes initial tissue damage, which initiates biochemical cascades, known as secondary injury, that expand the damage. Free radicals are implicated as major contributors to the secondary injury. Our review of recent rodent and human research reveals the prominent role of the free radicals superoxide anion, nitric oxide, and peroxynitrite in secondary brain injury. Much of our current knowledge is based on rodent studies, and the authors identified a gap in the translation of findings from rodent to human TBI. Rodent models are an effective method for elucidating specific mechanisms of free radical-induced injury at the cellular level in a well-controlled environment. However, human TBI does not occur in a vacuum, and variables controlled in the laboratory may affect the injury progression. Additionally, multiple experimental TBI models are accepted in rodent research, and no one model fully reproduces the heterogeneous injury seen in humans. Free radical levels are measured indirectly in human studies based on assumptions from the findings from rodent studies that use direct free radical measurements. Further study in humans should be directed toward large samples to validate the findings in rodent studies. Data obtained from these studies may lead to more targeted treatment to interrupt the secondary injury cascades.

The Role of Neuroimaging in Assessing Neuropsychological Deficits following Traumatic Brain Injury

2011 ◽  
Vol 39 (4) ◽  
pp. 537-566 ◽  
Author(s):  
Benjamin J. Hayempour ◽  
Susan E. Rushing ◽  
Abass Alavi
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Damage ◽  
Brain Injuries ◽  
Neuropsychological Deficits ◽  
Prognostic Information ◽  
Specific Identification ◽  
Secondary Damage ◽  
Neuroimaging Techniques

Neuroimaging enables highly accurate and specific identification of treatable brain injuries for the purposes of preventing secondary damage as well as providing useful prognostic information. This article addresses the range of currently employed neuroimaging techniques and their utility in assessing legal claims involving the presence of brain damage.

Differencial Diagnosis of Hypovolemia and Cushing‘s Response in Traumatic Brain Injury Patients, Using Hemodynamic Assessment Methods, to Prevent Secondary Brain Damage

2015 ◽  
Vol 25 (2) ◽  
pp. 83-86
Author(s):  
Giedrė Zinkevičiūtė Žarskienė ◽  
Diana Bilskienė ◽  
Andrius Macas
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Vegetative State ◽  
Public Health Problem ◽  
Morbidity And Mortality ◽  
Infusion Therapy ◽  
Secondary Brain Injury ◽  
Major Public Health Problem ◽  
Hemodynamic Assessment ◽  
Cord Injury

Traumatic brain injury is the leading cause of death and further cause of disability and a major public health problem. Although the severity of the injury depends directly on the primary brain injury, secondary brain injury deteriorates the outcomes. The main causes of secondary ischemic injury include hypotension (systolic blood pressure 90mmHg) and hypoxaemia (PaO260mmHg), which are directly associated with increase of morbidity and mortality due to severe traumatic brain injury. Hypoxia and hypotension during decompresive craniotomy are independently associated with significant increaeses in vegetative state development and higher frequency of disability. Intraoperative period, including immediate anaesthesia during urgent craniotomy, is a critical moment for these patients. Their intraoperative hypotension can be caused by various factors, such as blood loss due other traumatic injuries, direct pulmonary or heart disorders, sympathetic tone lesions (spinal cord injury and neurogenic shock), potent anesthetic medicaments action or current hypovolemia and inadequate infusion therapy. How to solve this situation? Usually we choose a larger infusion therapy and vasoactive drugs. Is it realy a best solution for the patient? Severe brain trauma and related complications are the most common morbidity and mortality causes in young and middle-aged people. The initial injury we can not influence, but to avoid the major secondary brain injury risks, especially such as hypotension and hypoxia, are required. Only quick and accurate diagnosis, secondary risk factors prevention and immediate treatment may improve the outcomes.

Endogenous opioids and electrolyte excretion after contralateral renal exclusion

1983 ◽  
Vol 244 (4) ◽  
pp. F392-F398 ◽  
Author(s):  
J. Ribstein ◽  
M. H. Humphreys
Keyword(s):  
Renal Mass ◽  
Opiate Receptors ◽  
Opiate Receptor ◽  
Endogenous Opioids ◽  
Subcutaneous Implantation ◽  
Electrolyte Excretion ◽  
Contralateral Kidney ◽  
Reflex Pathways ◽  
Ureteral Occlusion

Acute reductions in functioning renal mass result in increases in both sodium (U Na V) and potassium (U K V) excretion by the contralateral kidney (CK). We studied the role of endogenous opioids in this response. In control experiments acute unilateral nephrectomy (AUN) increased U Na V from 1,788 +/- 1,125 (SD) to 3,939 +/- 1,819 and U K V from 1,385 +/- 561 to 2,254 +/- 832 neq/min by the CK (P less than 0.005 for both); similar results occurred in rats undergoing acute unilateral ureteral occlusion (UUO). These increases occurred without overall change in GFR or mean arterial pressure. In rats receiving a continuous infusion of the opiate-receptor antagonist naloxone (0.3 mg . kg-1 . h-1) neither AUN nor UUO produced significant alterations in U Na V or U K V by the CK; naloxone infusion by itself did not alter GFR or basal rates of cation excretion. A separate group of rats was made tolerant to morphine by subcutaneous implantation of pellets containing 75 mg morphine base. In these rats, AUN also failed to produce any increase in U Na V or U K V by the CK. The results suggest that acute reductions in functioning renal mass produced by either AUN or UUO stimulate cation excretion by the remaining kidney through reflex pathways that involve opiate receptors.

scholarly journals Traumatic Brain Injury Patients Mortality and Serum Total Antioxidant Capacity

2020 ◽  
Vol 10 (2) ◽  
pp. 110 ◽  
Author(s):  
Leonardo Lorente ◽  
María M. Martín ◽  
Antonia Pérez-Cejas ◽  
Agustín F. González-Rivero ◽  
Pedro Abreu-González ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Antioxidant Capacity ◽  
Total Antioxidant Capacity ◽  
Injury Severity ◽  
Early Mortality ◽  
Secondary Brain Injury ◽  
Total Antioxidant ◽  
Time Of Admission

Objective: Oxidation is involved in secondary brain injury after traumatic brain injury (TBI). Increased concentrations of total antioxidant capacity (TAC) in blood at the time of admission for TBI have been found in non-surviving patients. The main objective of this study was to determine the role of serum TAC levels at any time during the first week of TBI for the prediction of early mortality. Methods: Isolated (<10 points in non-cranial aspects of Injury Severity Score) and severe (<9 points in Glasgow Coma Scale) TBI patients were included. Serum TAC concentrations at days 1, 4, and 8 of TBI were determined. The end-point study was 30-day mortality. Results: Higher serum TAC levels at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.002) of TBI were found in non-surviving (n = 34) than in surviving patients (n = 90). The area under curve (95% Confidence Interval) for prediction of 30-day mortality by serum TAC concentrations at days 1, 4, and 8 of TBI were 0.79 (0.71–0.86; p < 0.001), 0.87 (0.79–0.93; p < 0.001), and 0.76 (0.67–0.84; p = 0.006) respectively. Conclusions: The novelty of our study was the ability to predict 30-day mortality by serum TAC concentrations at any time during the first week of TBI.

The role of NLRP3 in traumatic brain injury and its regulation by pioglitazone

2020 ◽  
Vol 133 (4) ◽  
pp. 1083-1091
Author(s):  
Ho Jun Yi ◽  
Jung Eun Lee ◽  
Dong Hoon Lee ◽  
Young Il Kim ◽  
Chul Bum Cho ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Brain Edema ◽  
Cerebral Edema ◽  
Sham Group ◽  
Secondary Brain Injury ◽  
Treatment Groups ◽  
Perilesional Edema

OBJECTIVEPerilesional edema is a predominant mechanism underlying secondary brain injury after traumatic brain injury (TBI). Perilesional edema is characterized by inflammation, production of proinflammatory cytokines, and migration of peripheral immune cells into the brain. The nucleotide-binding domain and leucine-rich repeat (NLR) family pyrin domain–containing 3 protein (NLRP3) is a key component of secondary injury. Pioglitazone regulates NLRP3 and other inflammatory cytokines. In the present study, the role of NLRP3 and the pharmacological effects of pioglitazone were investigated in animal TBI models.METHODSBrain contusion was induced in a weight drop model involving 3 groups of mice: C57 BL/6 (sham group), NLRP3 knockout (K/O group), and pioglitazone-treated mice (treatment group). The percentage of brain water content of the 3 groups of mice was compared over a period of time. Western blot, immunohistochemistry, and immunofluorescence analyses were conducted to investigate NLRP3-related inflammasomes and the effects of pioglitazone in the TBI models.RESULTSBrain edema was the highest on day 3 after TBI in the sham group. Brain edema in both the K/O and the treatment groups was lower than in the sham group. In Western blot, the expression of inflammasomes was higher after TBI in the sham group, but the expression of interleukin-1β, caspase-1, and NLRP3 was decreased significantly following treatment with pioglitazone. The expression of GFAP (glial fibrillary acidic protein) and Iba1 was decreased in both the K/O and treatment groups. In addition, confocal microscopy revealed a decrease in microglial cell and astrocyte activation following pioglitazone therapy.CONCLUSIONSThe inflammasome NLRP3 plays a pivotal role in regulating cerebral edema and secondary inflammation. Interestingly, pioglitazone reduced cerebral edema and immune response after TBI by downregulating the effects of NLRP3. These results suggest that the clinical application of pioglitazone may be a neuroprotective strategy in TBI.

Neurosurgical Critical Care

2018 ◽  
Author(s):  
Jose Manuel Sarmiento ◽  
Shouri Lahiri
Keyword(s):  
Traumatic Brain Injury ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Critical Care ◽  
Brain Injury ◽  
Injury Severity ◽  
Secondary Brain Injury ◽  
Spinal Decompression ◽  
Cerebral Herniation ◽  
Cord Injury

The overarching goal of neurosurgical critical care is to prevent potential deleterious effects of secondary brain injury. The initial management of patients with traumatic brain injury prioritizes the assessment of injury severity and prevention of hypotension and hypoxemia. The assessment of severity in patients with traumatic brain injury is important for determining the need for intubation and need for placement of intracranial monitoring. The stepwise management of increased intracranial pressure following traumatic brain injury is emphasized to prevent cerebral herniation syndromes and cerebral infarcts. Treatment with glucocorticoids following acute spinal cord injury is not recommended. Operative indications for intracranial monitor placement, hemicraniectomy, and spinal decompression are reviewed.   This review contains 1 figure, 3 tables and 32 references Key Words: glucocorticoids in spinal cord injury, hemicraniectomy, intracranial hypertension, multimodal monitoring, secondary brain injury, spinal cord injury, spinal decompression, traumatic brain injury

Physical Rehabilitation in Minor Traumatic Injury or Concussion

2017 ◽  
Vol 14 (01) ◽  
pp. 056-058
Author(s):  
Carol DeMatteo ◽  
Himanshu Arora ◽  
Vivek Sharma
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Physical Therapy ◽  
Neck Pain ◽  
Traumatic Injury ◽  
Team Approach ◽  
Multidisciplinary Team Approach ◽  
Cognitive Rest ◽  
Postconcussion Symptoms

AbstractConcussion is a traumatic brain injury and can be caused by sports and non-sports related injuries. Most patients recover completely within days to several weeks; but, some patients continue to experience postconcussion symptoms including but not limited to headache, dizziness and neck pain. The mainstay of treatment for concussion in sports has been physical and cognitive rest until the acute symptoms abates. However, the window period for rest is currently being debated. For patients with persisting symptoms, longer than 1 month, multidisciplinary team approach is advisable. There is emerging evidence for the role of physical therapy as a treatment option in this population, especially for postconcussion symptoms.

scholarly journals Role of Melatonin in Traumatic Brain Injury and Spinal Cord Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Mehar Naseem ◽  
Suhel Parvez
Keyword(s):  
Traumatic Brain Injury ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Brain Injury ◽  
Protective Role ◽  
Secondary Injury ◽  
Severe Injuries ◽  
Cord Injury ◽  
Injured Part

Brain and spinal cord are implicated in incidences of two of the most severe injuries of central nervous system (CNS). Traumatic brain injury (TBI) is a devastating neurological deficit involving primary and secondary injury cascades. The primary and secondary mechanisms include complex consequences of activation of proinflammatory cytokines, cerebral edema, upregulation of NF-κβ, disruption of blood-brain barrier (BBB), and oxidative stress. Spinal cord injury (SCI) includes primary and secondary injury cascades. Primary injury leads to secondary injury in which generation of free radicals and oxidative or nitrative damage play an important pathophysiological role. The indoleamine melatonin is a hormone secreted or synthesized by pineal gland in the brain which helps to regulate sleep and wake cycle. Melatonin has been shown to be a versatile hormone having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties. It has a special characteristic of crossing BBB. Melatonin has neuroprotective role in the injured part of the CNS after TBI and SCI. A number of studies have successfully shown its therapeutic value as a neuroprotective agent in the treatment of neurodegenerative diseases. Here in this review we have compiled the literature supporting consequences of CNS injuries, TBI and SCI, and the protective role of melatonin in it.

scholarly journals Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention

2021 ◽  
Vol 12 ◽  
Author(s):  
Bin Yuan ◽  
Xiao-jie Lu ◽  
Qi Wu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Injury ◽  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Experimental Medicine ◽  
Secondary Brain Injury ◽  
Cns Injury ◽  
Cord Injury

Acute central nervous system (CNS) injuries, including stroke, traumatic brain injury (TBI), and spinal cord injury (SCI), are the common causes of death or lifelong disabilities. Research into the role of the gut microbiota in modulating CNS function has been rapidly increasing in the past few decades, particularly in animal models. Growing preclinical and clinical evidence suggests that gut microbiota is involved in the modulation of multiple cellular and molecular mechanisms fundamental to the progression of acute CNS injury-induced pathophysiological processes. The altered composition of gut microbiota after acute CNS injury damages the equilibrium of the bidirectional gut-brain axis, aggravating secondary brain injury, cognitive impairments, and motor dysfunctions, which leads to poor prognosis by triggering pro-inflammatory responses in both peripheral circulation and CNS. This review summarizes the studies concerning gut microbiota and acute CNS injuries. Experimental models identify a bidirectional communication between the gut and CNS in post-injury gut dysbiosis, intestinal lymphatic tissue-mediated neuroinflammation, and bacterial-metabolite-associated neurotransmission. Additionally, fecal microbiota transplantation, probiotics, and prebiotics manipulating the gut microbiota can be used as effective therapeutic agents to alleviate secondary brain injury and facilitate functional outcomes. The role of gut microbiota in acute CNS injury would be an exciting frontier in clinical and experimental medicine.

Sign in / Sign up

Export Citation Format

Share Document