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Results for “Traumatic Brain Injuries”

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PubMed1993

Investing in the comeback: parent's experience following traumatic brain injury.

The increasing incidence of survival following traumatic brain injury necessitates a closer examination of long-term care and caregiver issues. A sample of parents and brain-injured offspring from 20 families was explored to identify a qualitatively-generated theory describing the parent's experience following a brain-injured child's return to the home setting. The grounded theory methodology was used during data collection and analysis. All the brain-injured offspring had survived moderate to severe traumatic brain injury, were living with at least one parent, and were aged 17-34 years. Investing in the Comeback is the generated three-phase theory. These three phases--centering on, fostering independence and seeking stability describe the work of parents living with brain-injured offspring.

Adolescent↗

PubMed2003

Metabolic, neurochemical, and histologic responses to vibrissa motor cortex stimulation after traumatic brain injury.

During the prolonged metabolic depression after traumatic brain injury (TBI), neurons are less able to respond metabolically to peripheral stimulation. Because this decreased responsiveness has been attributed to circuit dysfunction, the present study examined the metabolic, neurochemical, and histologic responses to direct cortical stimulation after lateral fluid percussion injury (LFPI). This study addressed three specific hypotheses: that neurons, if activated after LFPI, will increase their utilization of glucose even during a period of posttraumatic metabolic depression; that this secondary activation results in an increase in the production of lactate and a depletion of extracellular glucose; and that because cells are known to be in a state of energy crisis after traumatic brain injury, additional energy demands resulting from activation can result in their death. The results indicate that stimulating to levels eliciting a vibrissa twitch resulted in an increase in the cerebral metabolic rate for glucose (CMR(glc); micromol.100 g(-1).min(-1)) of 34% to 61% in the sham-operated, 1-hour LFPI, and 7-day LFPI groups. However, in the 1-day LFPI group, stimulation induced a 161% increase in CMR(glc) and a 35% decrease in metabolic activation volume. Extracellular lactate concentrations during stimulation significantly increased from 23% in the sham-injured group to 55% to 63% in the 1-day and 7-day LFPI groups. Extracellular glucose concentrations during stimulation remained unchanged in the sham-injured and 7-day LFPI groups, but decreased 17% in the 1-day LFPI group. The extent of cortical degeneration around the stimulating electrode in the 1-day LFPI group nearly doubled when compared with controls. These results indicate that at 1 day after LFPI, the cortex can respond to stimulation with an increase in anaerobic glycolysis; however, this metabolic response to levels eliciting a vibrissa response via direct cortical stimulation appears to constitute a secondary injury in the TBI brain.

Animals↗

PubMed1997

Involvement of activation of dopaminergic neuronal system in learning and memory deficits associated with experimental mild traumatic brain injury.

Much evidence has indicated that a disturbance in dopamine neurotransmission following mild to moderate traumatic brain injury is involved in the development of post traumatic memory deficits. In the present study we examined the effects of a dopamine receptor agonist and some antagonists on latent learning and memory deficits associated with a concussive traumatic brain injury in mice. Anaesthetized animals were subjected to mild traumatic brain injury by dropping a weight onto the head, and a single-dose injection of apomorphine (0.3-3.0 mg/kg) or haloperidol (0.3-3.0 mg/kg) was made i.p. 15 min after the trauma. One week later, a water-finding task consisting of an acquisition trial, a retention test and a retest was employed to assess learning and memory functions. Mice that had received a traumatic brain injury were impaired in task performance, with prolonged latencies for finding and drinking in the retention test and retest. Administration of haloperidol but not of apomorphine significantly shortened the prolonged latency in both of the tests, indicating that antagonism of dopamine receptors is beneficial for the recovery of post traumatic memory deficits. In order to evaluate which receptor subtype plays the major role in this model, we examined the effects of SCH-23390 (0.03-0.3 mg/kg), a D1 receptor antagonist, and sulpiride (3.0-30 mg/kg), a D2 receptor antagonist, in the same experimental paradigm. The results showed that administration of sulpiride but not of SCH-23390 significantly improved the deficits in task performance, indicating that D2 receptors are the major site of action. However, combined treatment with SCH-23390 (0.03-0.3 mg/kg) and sulpiride (3.0 mg/kg) at doses that had no effect when the antagonists were given alone exerted a significant additive effect in improving these deficits, indicating that interaction between D1 and D2 receptors is involved in these processes. The present results suggest that a dopaminergic mechanism contributes to the memory dysfunction associated with traumatic brain injury.

Animals↗

PubMed1999

Adding insult to injury: the prognostic value of early secondary insults for survival after traumatic brain injury.

OBJECTIVES: To assess the prognostic value of summary measures of secondary physiological insult in addition to baseline clinical variables for patients with traumatic brain injury. METHODS: A series of 110 patients with traumatic brain injury had data on intracranial pressure (ICP), arterial blood pressure (ABP), cerebral perfusion pressure (CPP), arterial O2 saturation (SaO2), temperature in degrees C (Temp), and heart rate in beats/min (HRT) monitored and recorded every minute. Secondary insults were defined according to the Edinburgh University secondary insult grading system. The prognostic value of summary measures of these secondary insults was assessed by adding them to a prognostic model for survival at 1 year after controlling for baseline clinical variables using a previously validated model. RESULTS: Of the eight secondary insults measured, only ICP added significantly to the prediction of survival in the first 72 hours after injury. The particular type of summary measure did not seem to influence the results. After the addition of ICP to the model, none of the other secondary insult measures could improve the predictive power of the model significantly. CONCLUSIONS: Early intracranial hypertension is confirmed as a sign of poor prognosis in patients with traumatic brain injury, even after controlling for baseline clinical variables. The value or otherwise of treating such secondary insults, however, can only be definitively established in the context of prospective randomised controlled trials. The specific pathophysiological evolution of secondary insults is still the subject of much research, and a clear understanding will be necessary before the development of specific treatments is feasible.

Adult↗

PubMed2002

Axis I and II psychiatric disorders after traumatic brain injury: a 30-year follow-up study.

OBJECTIVE: Patients who had suffered traumatic brain injury were evaluated to determine the occurrence of psychiatric disorders during a 30-year follow-up. METHOD: Sixty patients were assessed on average 30 years after traumatic brain injury. DSM-IV axis I disorders were diagnosed on a clinical basis with the aid of the Schedules for Clinical Assessment in Neuropsychiatry (version 2.1), and axis II disorders were diagnosed with the Structured Clinical Interview for DSM-III-R Personality Disorders. Cognitive impairment was measured with a neuropsychological test battery and the Mini-Mental State Examination. RESULTS: Of the 60 patients, 29 (48.3%) had had an axis I disorder that began after traumatic brain injury, and 37 (61.7%) had had an axis I disorder during their lifetimes. The most common novel disorders after traumatic brain injury were major depression (26.7%), alcohol abuse or dependence (11.7%), panic disorder (8.3%), specific phobia (8.3%), and psychotic disorders (6.7%). Fourteen patients (23.3%) had at least one personality disorder. The most prevalent individual disorders were avoidant (15.0%), paranoid (8.3%), and schizoid (6.7%) personality disorders. Nine patients (15.0%) had DSM-III-R organic personality syndrome. CONCLUSIONS: The results suggest that traumatic brain injury may cause decades-lasting vulnerability to psychiatric illness in some individuals. Traumatic brain injury seems to make patients particularly susceptible to depressive episodes, delusional disorder, and personality disturbances. The high rate of psychiatric disorders found in this study emphasizes the importance of psychiatric follow-up after traumatic brain injury.

Adult↗

PubMedDate not supplied

Mild traumatic brain injury does not produce post-traumatic stress disorder.

It has been widely assumed that patients who sustain mild traumatic brain injury (MTBI) or post-concussive syndrome develop post-traumatic stress disorder (PTSD) in response to their cognitive difficulties, diminished coping skills, or other losses. This study examined 70 patients who had previously been diagnosed as having either PTSD or MTBI. Each patient was asked to provide a highly detailed chronological history of the events which preceded, followed, and occurred during the traumatic event, to indicate whether they were rendered unconscious or had amnesia for the event, and to describe the various symptoms they developed. All (100.0%) of the PTSD patients were able to provide a highly detailed and emotionally charged recollection of the events which occurred within 15 minutes of the traumatic event in comparison to none (0.0%) of the MTBI patients. None of the MTBI patients reported symptoms such as intrusive recollections of the traumatic event, nightmares, hypervigilance, phobic or startle reactions, or became upset when they were asked to describe the traumatic event or were exposed to stimuli associated with it. These data suggest that PTSD and MTBI are two mutually exclusive disorders, and that it is highly unlikely that MTBI patients develop PTSD symptoms. Furthermore, these findings suggest that clinicians should exercise considerable caution in ruling out PTSD prior to making the diagnosis of MTBI.

Adaptation, Psychological↗

PubMed2006

Decreased expression of glutamate transporters in astrocytes after human traumatic brain injury.

The primary mechanism for eliminating synaptically released glutamate is uptake by astrocytes. In the present study, we examined whether traumatic brain injury (TBI) affects the cellular expression of glutamate transporters EAAT1 and EAAT2. Morphometrical immunohistochemical analysis demonstrated a predominant expression of EAAT1 and EAAT2 in astrocytes of normal human neocortex (n = 10). Following traumatic injury of human brain (n = 55), the number of EAAT2-positive cells was decreased for a prolonged survival period within the traumatized neocortex and the pericontusional region. GFAP-positive astrocytes decreased in number within the first 24 h. Thereafter, the number of GFAP-positive astrocytes increased again, indicating formation of reactive gliosis. Double immunofluorescence examinations revealed a reduction in absolute numbers of GFAP-positive astrocytes coexpressing EAAT1 or EAAT2 at survival times up to 7 days. In addition, the relative fractions of astrocytes coexpressing glutamate transporters decreased following TBI. We conclude that the posttraumatic reduction in cellular EAAT 1 and EAAT2 expression is predominantly due to degeneration of astrocytes and to downregulation in surviving astrocytes. Our results support the view that reduced glutamate uptake by astrocytes contributes to posttraumatic elevation of extracellular glutamate in humans.

Adolescent↗

PubMed2002

Cerebrospinal fluid procalcitonin and severe traumatic brain injury in children.

OBJECTIVE: To determine the relationship between cerebrospinal fluid procalcitonin concentration and severe traumatic brain injury in children. DESIGN: Prospective, observational clinical study. SETTING: A multidisciplinary, tertiary-care pediatric intensive care unit. PATIENTS: Twenty-eight patients who required external ventricular drainage for management of severe traumatic brain injury (Glasgow Coma Scale score of <8) and 22 control patients for whom lumbar cerebrospinal fluid evaluation excluded possible meningitis. INTERVENTIONS: Standard intracranial pressure-directed neurointensive care, including intraventricular catheter placement and continuous cerebrospinal fluid drainage, was used to manage patients with severe traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Demographic data including age, mechanism of injury, time of injury, initial Glasgow Coma Scale score, and outcome were collected. Cerebrospinal fluid procalcitonin concentration was determined by immunoluminometric assay. Initial cerebrospinal fluid procalcitonin concentration (median [range]) in patients with severe traumatic brain injury was increased greater than three-fold vs. controls (0.41 ng/mL [0.15-2.14] vs. 0.12 ng/mL [0.00-0.24], p <.001). Initial cerebrospinal fluid procalcitonin concentration among patients with abusive head trauma (0.31 ng/mL [0.29-0.50]) also was increased vs. controls (p <.05), although this increase was less robust than patients with accidental trauma (0.41 ng/mL [0.15-2.14], p <.001 vs. controls). Additional examination of key demographic and outcome variables with a generalized linear regression model was performed for patients with severe traumatic brain injury. Univariate analysis revealed that both time after injury (p <.01) and abusive head trauma as a mechanism of injury (p <.001) were associated with attenuation of the increased cerebrospinal fluid procalcitonin response after traumatic brain injury. CONCLUSION: Cerebrospinal fluid procalcitonin concentration is increased in children after traumatic brain injury. The attenuated increase in cerebrospinal fluid procalcitonin among victims of abusive head trauma warrants further study because it may reflect impairment of endogenous neuroprotective mechanisms or delay in seeking medical attention. The significance of these observations remains to be determined as future studies elucidate the physiologic and mechanistic properties of procalcitonin.

Journal Article↗

PubMedDate not supplied

Mild traumatic brain injury: toward understanding manifestations and treatment.

Mild traumatic brain injury is misleading as a diagnostic term, as it may include a spectrum of manifestations ranging from transient mild symptoms to ongoing disabling problems. It is a source of significant economic burden to society in terms of days lost from work and costs related to medical treatment. Symptomatic individuals will frequently present to primary care general medical practitioners days, weeks, or even months after the trauma. General medical practitioners are thus put in the position of being the "gatekeepers" of medical care for such patients and become responsible for appropriate determination and authorization of medical tests, specialized referrals, and treatment. The purpose of this article, which is based on a review of the literature to 1997, is to provide physicians with an understanding of mild traumatic brain injury, including manifestations and treatment, as it occurs commonly and can significantly impact the quality of life of those affected.

Brain Concussion↗

PubMed2006

Osteogenic effects of traumatic brain injury on experimental fracture-healing.

BACKGROUND: Heterotopic bone formation has been observed in patients with traumatic brain injury; however, an association between such an injury and enhanced fracture-healing remains unclear. To test the hypothesis that traumatic brain injury causes a systemic response that enhances fracture-healing, we established a reproducible model of traumatic brain injury in association with a standard closed fracture and measured the osteogenic response with an in vitro cell assay and assessed bone-healing with biomechanical testing. METHODS: A standard closed femoral fracture was produced in forty-three Sprague-Dawley rats. Twenty-three of the rats were subjected to additional closed head trauma that produced diffuse axonal injury similar to that observed in patients with a traumatic brain injury. Twenty-one days after the procedure, all animals were killed and fracture-healing was assessed by measuring callus size and by mechanical testing. Sera from the animals were used in subsequent in vitro experiments to measure mitogenic effects on established cell lines of committed osteoblasts, fibroblasts, and mesenchymal stem cells. RESULTS: Biomechanical assessment demonstrated that the brain-injury group had increased stiffness (p = 0.02) compared with the fracture-only group. There was no significant difference in torsional strength between the two groups. Cell culture studies showed a significant increase in the proliferative response of mesenchymal stem cells after exposure to sera from the brain-injury group compared with the response after exposure to sera from the fracture-only group (p = 0.0002). This effect was not observed in fibroblasts or committed osteoblasts. CONCLUSIONS: These results support data from previous studies that have suggested an increased osteogenic potential and an enhancement of fracture-healing secondary to traumatic brain injury. Our results further suggest that the mechanism for this enhancement is related to the presence of factors in the serum that have a mitogenic effect on undifferentiated mesenchymal stem cells.

Animals↗

PubMed2004

Neuropsychological correlates of basal ganglia and medial temporal lobe NAA/Cho reductions in traumatic brain injury.

BACKGROUND: Proton magnetic resonance spectroscopy can assess neurochemical sequelae in traumatic brain injury. Metabolic abnormalities are present in the acute or subacute period in patients with traumatic brain injury and correlate with outcome on clinical scales. OBJECTIVE: To investigate the use of proton magnetic resonance spectroscopy in detecting possible gray subcortical neurochemical impairments and their relationship with neuropsychological performance. DESIGN: Group comparisons and correlations of brain metabolites with clinical and neuropsychological variables. PATIENTS AND METHODS: Metabolite concentrations were acquired from voxels localized to the basal ganglia and medial temporal region in 20 patients with long-term moderate and severe traumatic brain injury and 20 matched control subjects. Both groups underwent neuropsychological assessment. RESULTS: N-acetylaspartate-choline-containing compounds ratios were decreased in patients in the basal ganglia (t = -3.28, P =.002) and medial temporal region (t = -3.52, P =.001). The basal ganglia ratio correlated to measures of speed, motor scanning, and attention. CONCLUSION: Patients with long-term TBI present a regional correlation pattern that may help identify the neurological basis of cognitive sequelae in traumatic brain injury.

Adolescent↗

PubMed1989

Human glial cell production of lipoxygenase-generated eicosanoids: a potential role in the pathophysiology of vascular changes following traumatic brain injury.

Acute cerebrovascular changes which occur following traumatic brain injury represent a highly complex, multifactorial pathophysiologic process which is poorly understood. It is now recognized that, under normal conditions, the brain is a source of a variety of arachidonic acid metabolites which are synthesized by both cyclooxygenase and lipoxygenase. The specific cellular source of these highly vasoactive substances remains controversial. Recent work has demonstrated that lipoxygenase products were detected by immunosensitive assay in whole brain samples from a gerbil concussive injury model, yet the production of leukotrienes could not be accounted for by cerebral vessels and their contents alone. It has been theorized that the probable source for these metabolites is the cortical neuron. We sought to elucidate whether cultured human glial cells, obtained from specimens removed at the time of surgery, are a significant source of lipoxygenase products as measured by high performance liquid chromatography (HPLC). We observed that these cells consistently produced 5, 12, and 15-HETE class eicosanoids despite failure to produce significant cyclooxygenase products. These preliminary findings are of considerable interest because these lipoxygenase products are known to be highly vasoactive as well as potent mediators of increased vascular permeability. Since it is known that mechanical perturbation of cell membranes stimulates the release of arachidonic acid from membrane phospholipids, it is conceivable that the production of these eicosanoids following traumatic brain injury could account for local cerebrovascular changes including both vasospasm and interstitial edema formation.

Brain Injuries↗

PubMed2005

Brain death after severe traumatic brain injury: the role of systemic secondary brain insults.

Secondary brain insults predominantly due to hypotension are frequent among patients with fatal traumatic brain injury. We assessed the correlation between different systemic secondary brain insults and brain death in 404 patients admitted to our intensive care unit (ICU) after severe traumatic brain injury. We collated data on hypoxemia and hypotension prior to as well as the occurrence of hypoxemia, hypotension, shock, anemia, hyperglycemia, and hyperthermia within the first 24 hours after ICU admission. We also considered both the presence of extracranial injuries and the category of traumatic brain injury using computerized tomography. The 59 patients (14.6%) who developed brain death, were significantly older than patients without a fatal neurological outcome (46.1 +/- 22 vs 29.5 +/- 14.9 years; P < .0001). Intracranial mass lesions, whether surgically evacuated were more frequent among brain-dead patients. The systemic secondary brain insults significantly associated with brain death were hypoxemia, hypotension, shock, anemia, and hyperglycemia within the first 24 hours after ICU admission. After multivariate analysis, the factors that independently predicted brain death were the occurrence of shock (odds ratio [OR], 6.74; 95% confidence interval [CI], 2.85-15.84; P = .001) and older age (OR, 1.05; 95% CI, 1.03-1.07; P = .003). In conclusion, early shock seems to be the major systemic secondary brain insult associated with brain death in patients with severe traumatic brain injury. Prevention of or correction of shock might help to either decrease the occurrence of a fatal neurological outcome or in brain-dead patients to preserve organs in better condition for procurement.

Adult↗

PubMed1997

Temporal and regional patterns of axonal damage following traumatic brain injury: a beta-amyloid precursor protein immunocytochemical study in rats.

Diffuse axonal injury (DAI) is an important consequence of human head trauma. This experimental investigation utilized the immunocytochemical visualization of beta-amyloid precursor protein (beta-APP) to document regional patterns of axonal injury after traumatic brain injury (TBI) and to determine the importance of injury severity on the magnitude of axonal damage. Rats underwent moderate (1.84-2.11 atm) or severe (2.38-2.52 atm) parasagittal fluid-percussion (F-P) brain injury or sham procedures. At 1, 3, 7 or 30 days after TBI, rats were perfusion-fixed and sections immunostained for the visualization of beta-APP. A regionally specific axonal response to TBI was documented after moderate F-P injury. Within the dorsolateral striatum, an early increase in beta-APP-positive axonal profiles at 24 hours (h) was followed by a significant decline at subsequent survival periods. In contrast, the frequency of reactive profiles was initially low within the thalamus, but increased significantly by day 7. Within the external capsule at the injury epicenter, numbers of immunoreactive axons increased significantly at 24 h and remained elevated throughout the subsequent survival periods. At multiple periods after TBI, selective cortical and thalamic neurons displayed increased staining of the perikarya. A significant increase in the overall frequency of beta-APP profiles was documented in the severe vs moderately injured rats at 72 h after TBI. These data indicate that parasagittal F-P brain injury (a) results in widespread axonal damage, (b) that axonal damage includes both reversible and delayed patterns, and (c) that injury severity is an important factor in determining the severity of the axonal response to TBI.

Amyloid beta-Protein Precursor↗

PubMed2005

Effects of service delivery versus changes in incidence on trends in injury: a demonstration using hospitalised traumatic brain injury.

Though injury incidence and hospitalisations are likely to be correlated, a range of factors other than incidence of injury in a population may influence trends in hospitalised injuries. These include technical changes in the hospital data's coverage, and real changes in the incidence of hospitalisations independent of the population incidence. This paper addresses the latter using the example of traumatic brain injury (TBI) hospitalisations in New Zealand. Data were New Zealand public hospitals inpatient discharges. Five measures of TBI severity were used. The relative rate of minor to serious TBI hospitalisations declined by approximately 2-6% per year from 1988 to 1998. This decline is observed across different mechanisms and the two severity measures used in the detailed analysis. The relative decline in minor to serious TBI is likely to be related to a change in the probability of admission rather than a change in the population TBI incidence. As most TBI hospitalisations are minor this suggests the trend in TBI hospitalisations was significantly influenced by factors other than changes in population incidence. Any analysis of routinely collected secondary injury data needs to consider case selection carefully, especially if trends are being examined. Applying a severity threshold should give more reliable trends.

Adolescent↗

PubMed1990

Mitochondrial metabolism following traumatic brain injury in rats.

Although a number of studies of traumatic brain injury have implicated mitochondrial dysfunction as a cause of altered posttraumatic energy metabolism, no studies to date have isolated mitochondria and measured their respiratory capacity following trauma. The present study sought to determine whether mitochondrial capacity for oxidative phosphorylation is adversely affected by fluid-percussion-induced traumatic brain injury in rats. Prior to brain injury, the mitochondrial respiratory control ratio was 4.3 +/- 0.2 and the ratio of nmoles of ADP phosphorylated per natom oxygen consumed (ADP/O ratio) was 2.66 +/- 0.09. After injury (2.8 atm; t = 4 h), there were slight but not significant alterations in ADP/O ratio (2.41 +/- 0.07) and state 3 respiratory rate (ADP stimulated); however, there were no changes in the respiratory control ratio. These data suggest that traumatic brain injury, unlike ischemia, does not cause uncoupling of ATP synthesis from respiration, and that brain mitochondria are quite resistant to trauma-induced injury.

Adenosine Diphosphate↗

PubMed2004

Systematic search and review procedures: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.

The WHO Collaborating Centre for Neurotrauma Task Force on Mild Traumatic Brain Injury performed a comprehensive search and critical review of the literature published between 1980 and 2002 to assemble the best evidence on the epidemiology, diagnosis, prognosis and treatment of mild traumatic brain injury. Our primary sources of literature were Medline, Cinahl, PsycINFO and Embase. Citations were screened for relevance to mild traumatic brain injury, using a priori criteria, and relevant studies were critically reviewed for scientific merit. We identified 38,806 citations, of which 671 studies were judged relevant to the mandate of the task force. These, plus 70 studies found by hand-searching reference lists and 2 original research reports performed as part of the task force mandate were subjected to critical reviews. After review, 313 (42%) were accepted on scientific merit and comprise our best-evidence synthesis. Ninety percent of the literature on mild traumatic brain injury was found in Medline and another 5% in PsycINFO.

Advisory Committees↗

PubMed2003

Early neutrophilic expression of vascular endothelial growth factor after traumatic brain injury.

The formation of edema after traumatic brain injury (TBI) is in part associated with the disruption of the blood-brain barrier. However, the molecular and cellular mechanisms underlying these phenomena have not been fully understood. One possible factor involved in edema formation is vascular endothelial growth factor (VEGF). This growth factor has previously been demonstrated to increase the blood-brain barrier permeability to the low molecular weight markers and macromolecules. In this study, we analyzed the temporal changes in VEGF expression after TBI in rats. In the intact brain, VEGF was expressed at relatively low levels and was found in the cells located close to the cerebrospinal fluid space. These were the astrocytes located under the ependyma and the pia-glial lining, as well as the epithelial cells of the choroid plexus. In addition, several groups of neurons, including those located in the frontoparietal cortex and in all hippocampal regions, were VEGF-positive. The pattern of VEGF-immunopositive staining of neurons and choroidal epithelium suggested that in these cells, VEGF binds to the cell membrane-associated heparan sulfate proteoglycans. Following TBI, there was an early (within 4 h post-injury) increase in VEGF expression in the traumatized parenchyma associated with neutrophilic invasion. The ipsilateral choroid plexus appeared to play a role in facilitating the migration of neutrophils from blood into the cerebrospinal fluid space, from where many of these cells infiltrated the brain parenchyma. VEGF-immunopositive staining of neutrophils resembled haloes and was found ipsilaterally within the frontoparietal cortex and around the velum interpositum, a part of the subarachnoid space. These haloes likely represent the deposition of neutrophil-derived VEGF within the extracellular matrix, from where this growth factor may be gradually released during an early post-traumatic period. The maximum number of VEGF-secreting neutrophils was observed between 8 h and 1 day after TBI. In addition, from 4 h post-TBI, there was a progressive increase in the number of VEGF-immunoreactive astrocytes in the ipsilateral frontoparietal cortex. The maximum number of astrocytes expressing VEGF was observed 4 days after TBI, and then the levels of astroglial VEGF expression declined gradually. Early invasion of brain parenchyma by VEGF-secreting neutrophils together with a delayed increase in astrocytic synthesis of this growth factor correlate with the biphasic opening of the blood-brain barrier and formation of edema previously observed after TBI. Therefore, these findings suggest that VEGF plays an important role in promoting the formation of post-traumatic brain edema.

Animals↗