Platelet-activating factor and progressive brain damage following focal brain injury

1990 ◽  
Vol 73 (2) ◽  
pp. 223-233 ◽  
Author(s):  
Kai U. Frerichs ◽  
Perttu J. Lindsberg ◽  
John M. Hallenbeck ◽  
Giora Z. Feuerstein
Keyword(s):  
Brain Injury ◽  
Brain Damage ◽  
Neuronal Death ◽  
Hippocampal Neurons ◽  
Neuronal Damage ◽  
Platelet Activating Factor ◽  
Secondary Brain Damage ◽  
Content Type ◽  
Focal Brain Injury ◽  
Fine Print

✓ The effects of a platelet-activating factor (PAF) antagonist on brain edema, cortical microcirculation, blood-brain barrier (BBB) disruption, and neuronal death following focal brain injury are reported. A neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was used to induce highly reproducible focal cortical lesions in anesthetized rats. Secondary brain damage in this model was characterized by progressive cortical hypoperfusion, edema, and BBB disruption in the vicinity of the hemispheroid lesion occurring acutely after injury. The histopathological evolution was followed for up to 4 days. Neuronal damage in the cortex and the hippocampus (CA-1) was assessed quantitatively, revealing secondary and progressive loss of neuronal tissue within the first 24 hours following injury. Pretreatment with the PAF antagonist BN 50739 ameliorated the severe hypoperfusion in 12 rats (increasing local cerebral blood flow from a mean ± standard error of the mean of 40.5% ± 8.3% to 80.2% ± 7.8%, p < 0.01) and reduced edema by 70% in 10 rats (p < 0.05) acutely after injury. The PAF antagonist also reduced the progression of neuronal damage in the cortex and the CA-1 hippocampal neurons (decrease of neuronal death from 88.0% ± 3.9% to 49.8% ± 4.2% at 24 hours in the cortex and from 40.2 ± 5.0% to 13.2% ± 2.1% in the hippocampus in 30 rats; p < 0.05). This study provides evidence to support progressive brain damage following focal brain injury, associated with secondary loss of neuronal cells. In this latter process, PAF antagonists may provide significant therapeutic protection in arresting secondary brain damage following cerebral ischemia and neurological trauma.

Cytidinediphosphocholine treatment to decrease traumatic brain injury—induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction in rats

2003 ◽  
Vol 98 (4) ◽  
pp. 867-873 ◽  
Author(s):  
Robert J. Dempsey ◽  
Vemuganti L. Raghavendra Rao
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Death ◽  
Hippocampal Neurons ◽  
Neurological Dysfunction ◽  
Adult Rats ◽  
Edema Formation ◽  
Content Type ◽  
Cortical Contusion ◽  
Fine Print

Object. In previous studies at their laboratory the authors showed that cytidinediphosphocholine (CDP-choline), an intermediate of phosphatidylcholine synthesis, decreases edema formation and blood—brain barrier disruption following traumatic brain injury (TBI). In the present study the authors investigate whether CDP-choline protects hippocampal neurons after controlled cortical impact (CCI)—induced TBI in adult rats. Methods. After adult male Sprague—Dawley rats had been anesthetized with halothane, a moderate-grade TBI was induced with the aid of a CCI device set at a velocity of 3 m/second, creating a 2-mm deformation. Sham-operated rats, which underwent craniectomy without impact served as controls. The CDP-choline (100, 200, and 400 mg/kg body weight) or saline was injected into the animals twice (once immediately postinjury and once 6 hours postinjury). Seven days after the injury, the rats were neurologically evaluated and killed, and the number of hippocampal neurons was estimated by examining thionine-stained brain sections. By 7 days postinjury, there was a significant amount of neuronal death in the ipsilateral hippocampus in the CA2 (by 53 ± 7%, p < 0.05) and CA3 (by 59 ± 9%, p < 0.05) regions and a contusion (volume 34 ± 8 mm3) in the ipsilateral cortex compared with sham-operated control animals. Rats subjected to TBI also displayed severe neurological deficit at 7 days postinjury. Treating rats with CDP-choline (200 and 400 mg/kg, intraperitoneally) significantly prevented TBI-induced neuronal loss in the hippocampus, decreased cortical contusion volume, and improved neurological recovery. Conclusions. Treatment with CDP-choline decreased brain damage following TBI.

Hyperventilation early after controlled cortical impact augmented neuronal death in CA3 hippocampus

1998 ◽  
Vol 88 (3) ◽  
pp. 549-556 ◽  
Author(s):  
Michael L. Forbes ◽  
Robert S. B. Clark ◽  
C. Edward Dixon ◽  
Steven H. Graham ◽  
Donald W. Marion ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Neuronal Death ◽  
Hippocampal Neurons ◽  
Secondary Injury ◽  
Controlled Cortical Impact ◽  
Content Type ◽  
Beam Balance ◽  
Cortical Impact ◽  
Normal Ventilation ◽  
Fine Print

Minimizing secondary injury after severe traumatic brain injury (TBI) is the primary goal of cerebral resuscitation. For more than two decades, hyperventilation has been one of the most often used strategies in the management of TBI. Laboratory and clinical studies, however, have verified a post-TBI state of reduced cerebral perfusion that may increase the brain's vulnerability to secondary injury. In addition, it has been suggested in a clinical study that hyperventilation may worsen outcome after TBI. Object. Using the controlled cortical impact model in rats, the authors tested the hypothesis that aggressive hyperventilation applied immediately after TBI would worsen functional outcome, expand the contusion, and promote neuronal death in selectively vulnerable hippocampal neurons. Methods. Twenty-six intubated, mechanically ventilated, isoflurane-anesthetized male Sprague—Dawley rats were subjected to controlled cortical impact (4 m/second, 2.5-mm depth of deformation) and randomized after 10 minutes to either hyperventilation (PaCO2 = 20.3 ± 0.7 mm Hg) or normal ventilation groups (PaCO2 = 34.9 ± 0.3 mm Hg) containing 13 rats apiece and were treated for 5 hours. Beam balance and Morris water maze (MWM) performance latencies were measured in eight rats from each group on Days 1 to 5 and 7 to 11, respectively, after controlled cortical impact. The rats were killed at 14 days postinjury, and serial coronal sections of their brains were studied for contusion volume and hippocampal neuron counting (CA1, CA3) by an observer who was blinded to their treatment group. Mortality rates were similar in both groups (two of 13 in the normal ventilation compared with three of 13 in the hyperventilation group, not significant [NS]). There were no differences between the groups in mean arterial blood pressure, brain temperature, and serum glucose concentration. There were no differences between groups in performance latencies for both beam balance and MWM or contusion volume (27.8 ± 5.1 mm3 compared with 27.8 ± 3.3 mm3, NS) in the normal ventilation compared with the hyperventilation groups, respectively. In brain sections cut from the center of the contusion, hippocampal neuronal survival in the CA1 region was similar in both groups; however, hyperventilation reduced the number of surviving hippocampal CA3 neurons (29.7 cells/hpf, range 24.2–31.7 in the normal ventilation group compared with 19.9 cells/hpf, range 17–23.7 in the hyperventilation group [25th–75th percentiles]; *p < 0.05, Mann—Whitney rank-sum test). Conclusions. Aggressive hyperventilation early after TBI augments CA3 hippocampal neuronal death; however, it did not impair functional outcome or expand the contusion. These data indicate that CA3 hippocampal neurons are selectively vulnerable to the effects of hyperventilation after TBI. Further studies delineating the mechanisms underlying these effects are needed, because the injudicious application of hyperventilation early after TBI may contribute to secondary neuronal injury.

Factors affecting excitatory amino acid release following severe human head injury

1998 ◽  
Vol 89 (4) ◽  
pp. 507-518 ◽  
Author(s):  
Ross Bullock ◽  
Alois Zauner ◽  
John J. Woodward ◽  
John Myseros ◽  
Sung C. Choi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Brain Injury ◽  
Head Injury ◽  
Neuronal Damage ◽  
Cell Swelling ◽  
Glutamate Antagonists ◽  
Content Type ◽  
Fine Print

Object. Recent animal studies demonstrate that excitatory amino acids (EAAs) play a major role in neuronal damage after brain trauma and ischemia. However, the role of EAAs in patients who have suffered severe head injury is not understood. Excess quantities of glutamate in the extracellular space may lead to uncontrolled shifts of sodium, potassium, and calcium, disrupting ionic homeostasis, which may lead to severe cell swelling and cell death. The authors evaluated the role of EEAs in human traumatic brain injury. Methods. In 80 consecutive severely head injured patients, a microdialysis probe was placed into the gray matter along with a ventriculostomy catheter or an intracranial pressure (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were analyzed using high-performance liquid chromatography. Multifactorial analysis of the amino acid pattern was performed and its correlations with clinical parameters and outcome were tested. The levels of EAAs were increased up to 50 times normal in 30% of the patients and were significantly correlated to levels of structural amino acids both in each patient and across the whole group (p < 0.01). Secondary ischemic brain injury and focal contusions were most strongly associated with high EAA levels (27 ± 22 µmol/L). Sustained high ICP and poor outcome were significantly correlated to high levels of EAAs (glutamate > 20 µmol/L; p < 0.01). Conclusions. The release of EAAs is closely linked to the release of structural amino acids and may thus reflect nonspecific development of membrane micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate neuronal damage, and these patients may be the best candidates for treatment with glutamate antagonists in the future.

Repetitive transcranial magnetic stimulation for protection against delayed neuronal death induced by transient ischemia

2003 ◽  
Vol 99 (6) ◽  
pp. 1063-1069 ◽  
Author(s):  
Minoru Fujiki ◽  
Hidenori Kobayashi ◽  
Tatsuya Abe ◽  
Tohru Kamida
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Neuronal Death ◽  
Magnetic Stimulation ◽  
Neuronal Damage ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Ischemic Tolerance ◽  
Delayed Neuronal Death ◽  
Similar Degree ◽  
Content Type ◽  
Fine Print

Object. Data in the present study demonstrate that repetitive transcranial magnetic stimulation (rTMS) induces ischemic tolerance against delayed neuronal death (DND) of hippocampal neurons following an otherwise lethal ischemic insult. Methods. Various regimens of rTMS were delivered to adult gerbils at various times prior to an episode of ischemia induced by transient (5-minute) bilateral common carotid artery (CCA) occlusion. The extent of DND in the CA1 region of the hippocampus was assessed quantitatively 7 days after the transient ischemic episode. When rTMS was delivered 2 to 5 days prior to bilateral CCA occlusion, DND was substantially attenuated; delivery of rTMS 12 to 24 hours prior to occlusion induced partial tolerance. In the group of animals that had received stimulation 2 days prior to occlusion, neuron density in the CA1 sector was significantly higher (three gerbils, 210.33, 86.01% of normal) than in the group that experienced ischemia only (three gerbils, 10.66, 4.36% of normal). A similar degree of neuron sparing occurred when stimulation was delivered 3, 4, or 5 days prior to occlusion. Note that rTMS was effective when it was delivered at frequencies of 25 and 50 Hz. Stimulation at 25 Hz for 128 seconds (3200 pulses) was more effective than stimulation at 50 Hz for 64 seconds (3200 pulses) or 128 seconds (6400 pulses), however. Conclusions. Noninvasive rTMS represents an important tool for exploring the mechanisms of ischemic tolerance and preventing ischemic neuronal damage.

Artificial elevation of brain tissue glycerol by administration of a glycerol-containing agent

2001 ◽  
Vol 94 (4) ◽  
pp. 621-623 ◽  
Author(s):  
Kathrin König ◽  
Eckhard Rickels ◽  
Hans E. Heissler ◽  
Matthias Zumkeller ◽  
Madjid Samii
Keyword(s):  
Brain Damage ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Glycerol Concentration ◽  
Secondary Brain Damage ◽  
Left Frontal Lobe ◽  
Content Type ◽  
Blood Brain ◽  
Potential Marker ◽  
Fine Print

✓ In recent years the development of secondary brain damage and derangement of neurochemical parameters after severe head injury has been monitored using microdialysis. Provided the blood—brain barrier is intact, glycerol is regarded as a potential marker for membrane phospholipid degradation. The authors report a case in which marked elevation of interstitial glycerol was induced after exogenous administration of a glycerol-containing agent. A 25-year-old man was injured in a motorcycle accident and was admitted to the authors' institution with a unilateral dilated and fixed pupil and a Glasgow Coma Scale score of 3. Computerized tomography scans revealed a large subdural hematoma on the left side, subsequent midline shift, and generalized edema. Emergency craniotomy was performed for evacuation of the hematoma. The patient was prepared for multisensory monitoring and a microdialysis catheter was inserted into his left frontal lobe. After a routine enema containing 85% glycerol had been administered, the authors measured a marked increase in glycerol in the dialysate. This occurred while the patient was in as stable a condition as could be expected given the circumstances. The increase in interstitial glycerol in the injured tissue was most likely due to an impaired blood—brain barrier. Thus, the interstitial glycerol concentration had been corrupted by exogenous glycerol, and the marker properties of glycerol in this case became questionable. Consequently, administration of glycerol, which is frequently found in various infusions and emulsions, can promote secondary brain damage by adversely shifting osmotic gradients.

Angiographic demonstration of brain injury without significant mass lesion

1971 ◽  
Vol 35 (3) ◽  
pp. 296-302
Author(s):  
Glenn W. Kindt ◽  
Trygve O. Gabrielsen
Keyword(s):  
Brain Injury ◽  
Brain Damage ◽  
Vascular Changes ◽  
Content Type ◽  
Venous Filling ◽  
Luxury Perfusion ◽  
Angiographic Demonstration ◽  
Mass Lesions ◽  
Fine Print ◽  
Significant Mass

✓ Evidence of brain damage was demonstrated in two patients without significant mass lesions by the presence of early venous filling and abnormal contrast staining. The vascular changes were most prominent on subtraction films. It is likely that these angiograms demonstrated the “luxury perfusion” phenomenon described previously in areas of damaged brain.

Flushing in relation to a possible rise in intracranial pressure: documentation of an unusual clinical sign

2000 ◽  
Vol 92 (6) ◽  
pp. 1040-1044 ◽  
Author(s):  
Gregory W. Hornig
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Intraventricular Hemorrhage ◽  
Pneumococcal Meningitis ◽  
Clinical Importance ◽  
Neurological Deterioration ◽  
Content Type ◽  
Transient Nature ◽  
Fine Print

✓ This report documents clinical features in five children who developed transient reddening of the skin (epidermal flushing) in association with acute elevations in intracranial pressure (ICP). Four boys and one girl (ages 9–15 years) deteriorated acutely secondary to intracranial hypertension ranging from 30 to 80 mm Hg in the four documented cases. Two patients suffered from ventriculoperitoneal shunt malfunctions, one had diffuse cerebral edema secondary to traumatic brain injury, one was found to have pneumococcal meningitis and hydrocephalus, and one suffered an intraventricular hemorrhage and hydrocephalus intraoperatively. All patients were noted to have developed epidermal flushing involving either the upper chest, face, or arms during their period of neurological deterioration. The response was transient, typically lasting 5 to 15 minutes, and dissipated quickly. The flushing reaction is postulated to be a centrally mediated response to sudden elevations in ICP. Several potential mechanisms are discussed. Flushing has clinical importance because it may indicate significant elevations in ICP when it is associated with neurological deterioration. Because of its transient nature, the importance of epidermal flushing is often unrecognized; its presence confirms the need for urgent treatment.

Ischemic neuronal damage after acute subdural hematoma in the rat: effects of pretreatment with a glutamate antagonist

1991 ◽  
Vol 74 (6) ◽  
pp. 944-950 ◽  
Author(s):  
Min-Hsiung Chen ◽  
Ross Bullock ◽  
David I. Graham ◽  
Jimmy D. Miller ◽  
James McCulloch
Keyword(s):  
Brain Damage ◽  
Subdural Hematoma ◽  
Neuronal Damage ◽  
Nmda Receptor Antagonist ◽  
Acute Subdural Hematoma ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Content Type ◽  
Irreversible Brain Damage ◽  
Slow Injection

✓ The ability of a competitive N-methyl-D-aspartate (NMDA) receptor antagonist (D-CPP-ene) to reduce irreversible brain damage has been examined in a rodent model of acute subdural hematoma. Acute subdural hematoma was produced by the slow injection of 400 µl homologous blood into the subdural space overlying the parietal cortex in halothane-anesthetized rats. Brain damage was assessed histologically in sections at multiple coronal planes in animals sacrificed 4 hours after induction of the subdural hematoma. Pretreatment with D-CPP-ene (15 mg/kg) significantly reduced the volume of ischemic brain damage produced by the subdural hematoma from 62 ± 8 cu mm (mean ± standard error of the mean) in vehicle-treated control rats to 29 ± 7 cu mm in drug-treated animals. These data demonstrate the anti-ischemic efficacy of NMDA antagonists in an animal model of intracranial hemorrhage in which intracranial pressure is elevated, and suggest that excitotoxic mechanisms (which are susceptible to antagonism by D-CPP-ene) may play a role in the ischemic brain damage which is observed in patients who die after acute subdural hematoma.

scholarly journals Inhaled Nitric Oxide Reduces Secondary Brain Damage after Traumatic Brain Injury in Mice

2012 ◽  
Vol 33 (2) ◽  
pp. 311-318 ◽  
Author(s):  
Nicole A Terpolilli ◽  
Seong-Woong Kim ◽  
Serge C Thal ◽  
Wolfgang M Kuebler ◽  
Nikolaus Plesnila
Keyword(s):  
Nitric Oxide ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Damage ◽  
Brain Regions ◽  
Lesion Volume ◽  
Effective Treatment Option ◽  
Secondary Brain Damage ◽  
Edema Formation ◽  
Regional Ischemia

Ischemia, especially pericontusional ischemia, is one of the leading causes of secondary brain damage after traumatic brain injury (TBI). So far efforts to improve cerebral blood flow (CBF) after TBI were not successful because of various reasons. We previously showed that nitric oxide (NO) applied by inhalation after experimental ischemic stroke is transported to the brain and induces vasodilatation in hypoxic brain regions, thus improving regional ischemia, thereby improving brain damage and neurological outcome. As regional ischemia in the traumatic penumbra is a key mechanism determining secondary posttraumatic brain damage, the aim of the current study was to evaluate the effect of NO inhalation after experimental TBI. NO inhalation significantly improved CBF and reduced intracranial pressure after TBI in male C57 Bl/6 mice. Long-term application (24 hours NO inhalation) resulted in reduced lesion volume, reduced brain edema formation and less blood–brain barrier disruption, as well as improved neurological function. No adverse effects, e.g., on cerebral auto-regulation, systemic blood pressure, or oxidative damage were observed. NO inhalation might therefore be a safe and effective treatment option for TBI patients.

Cerebral acid-base and gas metabolism in brain injury

1970 ◽  
Vol 33 (5) ◽  
pp. 498-505 ◽  
Author(s):  
R. Zupping
Keyword(s):  
Metabolic Acidosis ◽  
Brain Injury ◽  
Brain Damage ◽  
Close Correlation ◽  
Respiratory Alkalosis ◽  
Acid Base ◽  
Content Type ◽  
Arterial Blood ◽  
Gas Metabolism ◽  
Permanent Brain Damage

✓ Acid-base and gas parameters of CSF, jugular venous and arterial blood were measured in 45 patients with brain injury in the first 12 days after trauma or operation. CSF metabolic acidosis together with respiratory alkalosis and hypoxemia in the cerebral venous and arterial blood were the most characteristic findings. A close correlation between the severity of brain damage and the intensity of the CSF metabolic acidosis and arterial hypocapnia was revealed. It was concluded that brain hypoxia and acidosis play an important role in the development of cerebral edema and permanent brain damage.

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