The effect of groups II and III metabotropic glutamate receptor activation on neuronal injury in a rodent model of traumatic brain injury.

OBJECTIVE: The role of metabotropic glutamate receptor activation after traumatic brain injury (TBI) is not well understood. In vitro studies suggest that activation of Groups II and III metabotropic glutamate receptors may provide some degree of neuroprotection and may be potential targets for the development of therapeutic strategies. Thus, we examined the effects of Group II and Group III selective agonists on neuronal degeneration after in vivo TBI. METHODS: Fifty male Sprague-Dawley rats were subjected to lateral fluid percussion brain injury immediately followed by an intracranial injection of 2-(2',3')-dicarboxycyclopropylglycine (DCG-IV) (Group II) or (R,S)-4-phosphonophenylglycine (Group III) in the CA2 and CA3 areas of the hippocampus. DCG-IV was injected at doses of 20 fmol, 100 fmol, and 500 fmol, and (R,S)-4-phosphonophenylglycine was injected at 8 nmol, 40 nmol, and 200 nmol. Vehicle injection control groups were used for comparison with each drug group. All animals were killed 24 hours after TBI was induced. Four 50-microm brain sections were obtained from each animal and stained for degenerating neurons with the fluorochrome Fluoro-Jade. Two independent, blinded investigators counted the number of degenerating (Fluoro-Jade-positive) neurons in the CA2 and CA3 areas of the hippocampus of each brain section. RESULTS: Compared with vehicle, the 500-fmol dose of DCG-IV significantly reduced the number of Fluoro-Jade-positive degenerating neurons (P < 0.001). Lower doses of DCG-IV were associated with a decreased but not statistically significant number of Fluoro-Jade-positive neurons. In contrast, (R,S)-4-phosphonophenylglycine had no significant effect on the number of degenerating neurons. CONCLUSION: Administration of selective Group II metabotropic glutamate receptor agonists protects neurons against in vivo TBI. These receptors may thus be a promising target for future neuroprotective drugs.

Cerebral perfusion and blood flow in neurotrauma.

Post-traumatic cerebral ischemia is associated with a poor prognosis. Optimization of cerebral perfusion and blood flow thus plays a key role in contemporary head injury management. However, understanding of the pathophysiology of severe head injury is required for optimal patient management. This article explains the relationships between cerebral blood flow and metabolism and summarizes the current understanding of how these parameters can be helpful in the treatment of patients with severe head injuries.

Subarachnoid haemorrhage following rupture of an ophthalmic artery aneurysm presenting as traumatic brain injury.

Head trauma may provoke subarachnoid haemorrhage. The question sometimes arises whether in patients with trauma and subarachnoid haemorrhage the latter is of traumatic or aneurysmal origin. We present a 49-year-old patient who fell from a truck, struck his head and was unconscious immediately. On the brain computed tomography (CT) scan subarachnoid haemorrhage was present, initially diagnosed as of traumatic origin. Four-vessel angiography revealed rupture of a left ophthalmic artery aneurysm. We review the literature and give recommendations for angiography in patients with trauma and subarachnoid haemorrhage.

ICP monitoring in the rat: comparison of monitoring in the ventricle, brain parenchyma, and cisterna magna.

Various methods of continuous intracranial pressure (ICP) monitoring during experimental procedures in the rat have been described. However, no systematic comparison of ICP monitoring in the ventricle, brain parenchyma, and cisterna magna has been reported. Since accurate and reliable ICP measurements are important in experimental models of traumatic brain injury, the present study was conducted to compare simultaneous ICP measurements from ventricular, cisterna magna, and intraparenchymal monitors during ICP changes. Subdural hematoma was produced by infusion of 0.3 ml of autologous blood into the subdural space over 6 min. The ventricular and the intraparenchymal fiberoptic catheter produced reliable and comparable pressure recordings, that did not statistically differ (p = 0.4), throughout the one hour monitoring time. In contrast, the cisterna magna catheter was less reliable and produced significantly lower readings throughout the monitoring time (p<0.001). The intraparenchymal device produced greater cortical damage than the ventricular catheter. In conclusion, ventricular ICP monitoring is the preferred method under these circumstances, since it is accurate and induces least brain damage.

Severe pediatric head injury: the role of hyperemia revisited.

Diffuse cerebral swelling is a frequent finding after severe pediatric head injury, and is two to five times as common in children as in adults. Hyperemia or cerebrovascular engorgement has long been considered by many as the cause of diffuse swelling and raised intracranial pressure (ICP). Consequently, reduction of the vascular compartment by institution of hyperventilation and avoidance of mannitol has been advocated for the intensive care management of severely head-injured children. Suzuki and colleagues (1990) studied cerebral blood flow (CBF) in 80 normal, unanesthetized children. It was shown that CBF in normal children may range from 40 mL/100 g per minute during the first 6 months of life to a peak of 108 mL/100 g per minute at age 3 to 4 years, and down to 71 mL/100 g per minute after age 9 years. Considering this large range, comparisons of CBF data in children are valid only when small, well-defined age ranges are selected. When the CBF values of children with severe head injuries (described in previous research) were compared with normal values in children, there did not seem to be a substantial increase of CBF. Hyperemia may therefore not be as common in severe pediatric head injury as previously thought. Until we acquire a better understanding of the pathophysiology of severe pediatric head injury, and what the optimal treatment in children would be, there is no reason to treat children differently from adults.

The prognostic importance of the volume of traumatic epidural and subdural haematomas revisited.

The size of a traumatic intracranial haematoma at the moment of diagnosis can be impressive. Haematoma thickness is an inaccurate estimator of haematoma volume, and association with patient outcome is controversial. In this study computerized volumetry of offline digitized CT scans was used to relate haematoma volume with both patient characteristics on admission and at the six months outcome. This retrospective study covered the time period 1981/1990. Ninety eight patients operated upon for an epidural haematoma and 91 patients operated upon for an acute subdural haematoma were analyzed. The relative importance of clinical data, CT scan parameters, and calculated haematoma volumes was determined by multivariate analysis. Volume of the haematoma did not correlate with preoperative neurological condition or the six months outcome in either group, and consequently is not of additional prognostic value.

The prophylactic use of transluminal balloon angioplasty in patients with Fisher Grade 3 subarachnoid hemorrhage: a pilot study.

OBJECT: Recent advances in neuroradiology have made it possible to dilate vasospastic human cerebral arteries after aneurysmal subarachnoid hemorrhage (SAH), but the time window is short and the success rate for reversal of delayed ischemic neurological deficits (DINDs) varies between 31% and 77%. In a dog model of vasospasm, transluminal balloon angioplasty (TBA) performed on Day 0 totally prevented the development of angiographically demonstrated narrowing on Day 7. Because the effect of preventive TBA in this animal model was better than any pharmacological treatment described previously for experimental vasospasm, the authors conducted a pilot trial in humans to assess the safety and efficacy of TBA performed within 3 days of SAH. METHODS: The study group consisted of 13 patients with Fisher Grade 3 SAH who had a very high probability of developing vasospasm. In all patients, regardless of the site of the ruptured aneurysm, target vessels for prophylactic TBA were as follows: the internal carotid artery, A1 segment, M1 segment, and P1 segment bilaterally; the basilar artery; and one vertebral artery. Prophylactic TBA was considered satisfactory when it could be performed in at least two of the three parts of the intracranial circulation (right and/or left carotid system and/or vertebrobasilar system), and included the aneurysm-bearing part of the circulation. Of the 13 patients, none developed a DIND or more than mild vasospasm according to transcranial Doppler ultrasonography criteria. At 3 months posttreatment eight patients had made a good recovery, two were moderately disabled, and three had died; one patient died because of a vessel rupture during TBA and two elderly individuals died of medical complications associated with poor clinical condition on admission. CONCLUSIONS: Compared with large series of patients with aneurysmal SAH reported in the literature, the results of this pilot study indicate an extremely low incidence of vasospasm and DIND after treatment with prophylactic TBA. A larger randomized study is required to determine whether prophylactic TBA is efficacious enough to justify the risks, and which vessels need to be dilated prophylactically.

Safety and efficacy of transluminal balloon angioplasty in the prevention of vasospasm in patients with Fisher Grade 3 subarachnoid hemorrhage: a pilot study.

Recent advances in neuroradiology have made it possible to dilate human cerebral arteries that show vasospasm following aneurysmal subarachnoid hemorrhage (SAH), but the time window is short and the success rate for reversal of delayed ischemic neurological deficit (DIND) varies between 31% and 77%. In a canine model of vasospasm, transluminal balloon angioplasty (TBA) performed on Day 0 (the day of aneurysm rupture) has been shown to completely prevent the development of angiographically demonstrated narrowing by Day 7; this effect is better than any pharmacological treatment for vasospasm thus far described. The authors conducted a pilot trial to assess the safety and efficacy of TBA performed within 3 days post-SAH. Twelve patients with a very high probability of developing vasospasm (Fisher Grade 3) were included. Target vessels for prophylactic TBA were the internal carotid artery, A1 segment, M1 segment, and P1 segment bilaterally, the basilar artery, and the vertebral artery. No patient developed DIND or more than mild vasospasm, according to transcranial Doppler criteria. At 3 months, seven patients made a good recovery, two patients were moderately disabled, and three patients died; one patient died because of a vessel rupture during TBA and two older patients died of medical complications associated with an already poor clinical condition at admission. Compared with the results of large series reported in literature of patients with aneurysmal SAH, the results of this pilot study indicate an extremely low incidence of vasospasm and DIND after patients underwent prophylactic TBA. A larger, randomized study, however, is required to determine whether prophylactic TBA is efficacious enough to justify the risks.