Hyperbaric Oxygen Therapy Alleviates Memory and Motor Impairments Following Traumatic Brain Injury via the Modulation of Mitochondrial-Dysfunction-Induced Neuronal Apoptosis in Rats.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young adults, characterized by primary and secondary injury. Primary injury is the immediate mechanical damage, while secondary injury results from delayed neuronal death, often linked to mitochondrial damage accumulation. Hyperbaric oxygen therapy (HBOT) has been proposed as a potential treatment for modulating secondary post-traumatic neuronal death. However, the specific molecular mechanism by which HBOT modulates secondary brain damage through mitochondrial protection remains unclear. Spatial learning, reference memory, and motor performance were measured in rats before and after Controlled Cortical Impact (CCI) injury. The HBOT (2.5 ATA) was performed 4 h following the CCI and twice daily (12 h intervals) for four consecutive days. Mitochondrial functions were assessed via high-resolution respirometry on day 5 following CCI. Moreover, IHC was performed at the end of the experiment to evaluate cortical apoptosis, neuronal survival, and glial activation. The current result indicates that HBOT exhibits a multi-level neuroprotective effect. Thus, we found that HBOT prevents cortical neuronal loss, reduces the apoptosis marker (cleaved-Caspase3), and modulates glial cell proliferation. Furthermore, HBO treatment prevents the reduction in mitochondrial respiration, including non-phosphorylation state, oxidative phosphorylation, and electron transfer capacity. Additionally, a superior motor and spatial learning performance level was observed in the CCI group treated with HBO compared to the CCI group. In conclusion, our findings demonstrate that HBOT during the critical period following the TBI improves cognitive and motor damage via regulating glial proliferation apoptosis and protecting mitochondrial function, consequently preventing cortex neuronal loss.

HBO treatment enhances motor function and modulates pain development after sciatic nerve injury via protection the mitochondrial function.

BACKGROUND: Peripheral nerve injury can cause neuroinflammation and neuromodulation that lead to mitochondrial dysfunction and neuronal apoptosis in the dorsal root ganglion (DRG) and spinal cord, contributing to neuropathic pain and motor dysfunction. Hyperbaric oxygen therapy (HBOT) has been suggested as a potential therapeutic tool for neuropathic pain and nerve injury. However, the specific cellular and molecular mechanism by which HBOT modulates the development of neuropathic pain and motor dysfunction through mitochondrial protection is still unclear. METHODS: Mechanical and thermal allodynia and motor function were measured in rats following sciatic nerve crush (SNC). The HBO treatment (2.5 ATA) was performed 4 h after SNC and twice daily (12 h intervals) for seven consecutive days. To assess mitochondrial function in the spinal cord (L2-L6), high-resolution respirometry was measured on day 7 using the OROBOROS-O2k. In addition, RT-PCR and Immunohistochemistry were performed at the end of the experiment to assess neuroinflammation, neuromodulation, and apoptosis in the DRG (L3-L6) and spinal cord (L2-L6). RESULTS: HBOT during the early phase of the SNC alleviates mechanical and thermal hypersensitivity and motor dysfunction. Moreover, HBOT modulates neuroinflammation, neuromodulation, mitochondrial stress, and apoptosis in the DRG and spinal cord. Thus, we found a significant reduction in the presence of macrophages/microglia and MMP-9 expression, as well as the transcription of pro-inflammatory cytokines (TNFa, IL-6, IL-1b) in the DRG and (IL6) in the spinal cord of the SNC group that was treated with HBOT compared to the untreated group. Notable, the overexpression of the TRPV1 channel, which has a high Ca2+ permeability, was reduced along with the apoptosis marker (cleaved-Caspase3) and mitochondrial stress marker (TSPO) in the DRG and spinal cord of the HBOT group. Additionally, HBOT prevents the reduction in mitochondrial respiration, including non-phosphorylation state, ATP-linked respiration, and maximal mitochondrial respiration in the spinal cord after SNC. CONCLUSION: Mitochondrial dysfunction in peripheral neuropathic pain was found to be mediated by neuroinflammation and neuromodulation. Strikingly, our findings indicate that HBOT during the critical period of the nerve injury modulates the transition from acute to chronic pain via reducing neuroinflammation and protecting mitochondrial function, consequently preventing neuronal apoptosis in the DRG and spinal cord.

Skull base hemangiopericytomas.

OBJECTIVE: To retrospectively evaluate the clinical outcome of six patients with skull base hemangiopericytomas (HPCs) and that of a cohort of 37 similar patients identified by a systematic review of the literature. METHODS: The series constitutes of three men and three women with newly diagnosed skull base HPC who underwent multimodal treatment including surgery, external beam radiotherapy (EBRT) and pre-operative embolization. Furthermore, a systematic review off the literature identified 37 reports of primarily intracranial skull base HPCs. RESULTS: Four patients had a gross total resection (GTR) and two patients had a near total resection. Five patients were referred for adjuvant EBRT with a survival ranging from 15 to 47 months. All patients had an excellent outcome and resumed their previous activities. Literature review identified 37 additional patients with skull base HPC. Altogether, tumors were unevenly distributed above and below tentorium. GTR was achieved in half the patients, and 72.1% were referred to EBRT. Out of 37 reported patients in the literature, survival longer than 1 year was described in only 24. Within the combined cohort including the present series, survival was 83.6 months. CONCLUSIONS: The present series shows that a radical resection of HPC can be achieved under the difficult anatomical conditions of skull base surgery. Pre-operative arterial embolization may be instrumental to maintain a clear visual field and prevent excessive blood loss. Finally, the results of the present cohort suggest that EBRT may be useful for local growth control, as an effective palliative measure for skull base HPCs.

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

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.

IgG4-related pachymeningitis masquerading as foramen magnum meningioma: illustrative case.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated inflammatory condition with potential multiorgan involvement. Common manifestations include autoimmune pancreatitis and retroperitoneal fibrosis. Pathological analysis reveals lymphoplasmacytic infiltrate rich in IgG4-positive cells and characteristic storiform fibrosis. Early treatment with glucocorticoids may prevent progression to poorly responsive fibrotic disease. OBSERVATIONS: A 63-year-old female patient presented with reports of left-sided headaches, nausea, and photophobia in addition to recently diagnosed chronic rhinosinusitis (CRS). Neurological examination revealed dysarthria secondary to left hypoglossal nerve palsy. Computed tomography (CT) revealed a contrast-enhancing extraaxial mass at the left craniocervical junction, CRS with secondary hyperostotic reaction, and multiple hypodense lesions involving the occipital bone. Magnetic resonance imaging revealed a dural-based lesion involving the foramen magnum and invading the left hypoglossal canal. The patient underwent a far-lateral craniotomy. Histopathological analysis revealed severe lymphoplasmacytic inflammation, storiform fibrosis and rich plasma-cell population positive for IgG4. Serum IgG4 was markedly elevated. Total-body CT showed no systemic involvement. The patient was diagnosed with IgG4-RD and was prescribed prednisone, with normalization of her IgG4 levels after 1 month. LESSONS: IgG4-RD may mimic a variety of diseases, including skull-base meningiomas and CRS. Accurate diagnosis and expedited administration of steroids may prevent unnecessary interventions and progression to treatment-resistant fibrosis.

Reduction of Traumatic Brain Damage by Tspo Ligand Etifoxine.

Experimental studies have shown that ligands of the 18 kDa translocator protein can reduce neuronal damage induced by traumatic brain injury by protecting mitochondria and preventing metabolic crisis. Etifoxine, an anxiolytic drug and 18 kDa translocator protein ligand, has shown beneficial effects in the models of peripheral nerve neuropathy. The present study investigates the potential effect of etifoxine as a neuroprotective agent in traumatic brain injury (TBI). For this purpose, the effect of etifoxine on lesion volume and modified neurological severity score at 4 weeks was tested in Sprague-Dawley adult male rats submitted to cortical impact contusion. Effects of etifoxine treatment on neuronal survival and apoptosis were also assessed by immune stains in the perilesional area. Etifoxine induced a significant reduction in the lesion volume compared to nontreated animals in a dose-dependent fashion with a similar effect on neurological outcome at four weeks that correlated with enhanced neuron survival and reduced apoptotic activity. These results are consistent with the neuroprotective effect of etifoxine in TBI that may justify further translational research.

Post-traumatic cytotoxic edema is directly related to mitochondrial function.

Cerebral edema represents a major threat following traumatic brain injury. However, therapeutic measures for control of intracranial pressure alone have failed to restore cerebral metabolism and improve neurological outcome. Since mitochondrial damage results in ATP depletion and deactivation of membrane ionic pumps, we hypothesized that modulation of ATP bioavailability may directly affect cytotoxic edema. Intracranial pressure measurements were performed in Sprague-Dawley rats treated by intraperitoneal injection of dimethylsulfoxide (vehicle), cyclosporine A (CsA), or Oligomycin B (OligB) following cortical contusion and further correlated with water content, mitochondrial damage, and electron microscopic assessment of neuronal and axonal edema. As hypothesized, ultra-structural figures of edema closely correlated with intracranial pressure elevation, increased water content and mitochondrial membrane permeabilization expressed by loss of transmembrane mitochondrial potential. Further, mitochondrial damage evidenced ultra-structurally by figures of swollen mitochondria with severely distorted cristae correlated with both cytotoxic edema and mitochondrial dysfunction. Importantly, cerebral edema and mitochondrial impairment were significantly worsened by treatment with OligB, whereas a noticeable improvement could be observed in animals that received injections of CsA. Since OligB and CsA are responsible for symmetrical and opposite effects on oxidative metabolism, these findings support the hypothesis of a causative relationship between edema and mitochondrial function.

Investigation of the mechanisms of neuroprotection mediated by Ro5-4864 in brain injury.

Increasing evidence has established the involvement of the 18-kDa translocator protein (TSPO) in the process of mitochondrial membrane permeabilization and subsequent apoptosis through modulation of the mitochondrial permeability transition pore. Recent studies have shown that treatment with Ro5-4864, a TSPO ligand, resulted in a neuroprotective effect in traumatic brain injury. Yet, the nature of this effect remained uncertain as mature neurons are considered to be lacking the TSPO protein. In order to investigate the mechanism of Ro5-4864-mediated neuroprotection, the neuro-inflammatory and neurosteroid response to cortical injury was tested in sham-operated, vehicle, cyclosporine A (CsA) and Ro5-4864-treated rats. As anticipated, the levels of interleukin 1ß and tumor necrosis factor α, as well as the astrocyte and microglia cellular density in the injured area were all decreased by CsA in comparison with the vehicle group. By contrast, no visible effect could be observed in Ro5-4864-treated animals. None of the groups showed any significant difference with any other in respect with the expression of brain-derived neurotrophic factor. Double immunofluorescence staining with NeuN and TSPO confirmed the absence of TSPO in native neurons though showed clear evidence of co-localization of TSPO in the cytoplasm of NeuN-stained injured neurons. Altogether, this study shows that the neuronal protection mediated by Ro5-4864 in brain injury cannot be solely attributed to an indirect effect of the ligand on glial TSPO but may also represent the consequence of the modulation of upregulated TSPO in injured neurons. This observation may be of importance for future pharmacological research in neurotrauma.

Syria civil war: Outcomes of humanitarian neurosurgical care provided to Syrian wounded refugees in Israel.

BACKGROUND: As an expected consequence of the civil war in Syria, emergent neurosurgical care for battlefield trauma has been provided for severely head-injured Syrians transferred to Northern Israel. METHODS: Sixty-six patients suffering from brain injury were brought to the border and then referred to the institution after initial resuscitation. Both the time and type of injury were recorded based on paramedic testimony, forensic material or on details provided by patients. A retrospective analysis of all medical charts and imaging material was performed. RESULTS: Most injuries were combat-related, either caused by blast (13.6%), shrapnel (24.2%), assault (28.8%) or gunshot wound (15.2%). Only a minority of patients (18.2%) suffered from injuries that were not directly caused by weapon. A total of 55 surgical procedures were performed in 46 out of 66 patients, including craniotomies in 40 patients, burr hole alone for placement of intraparenchymal intracranial pressure (ICP) sensor in nine instances and ventricle peritoneal shunt in two patients. Decompressive craniectomy was used only for the treatment of gunshot wound and was performed in eight out of 10 patients. The most common complication consisted in cerebrospinal fluid fistulas (16.7%). Post-operative infections occurred in seven patients (10.6%). Short-term outcomes were favourable in 60.7%, with a mortality rate of 4.5%. DISCUSSION: The present findings suggest that aggressive surgery and neuro-intensive care measures may lead to good functional results, even in the presence of seemingly devastating injuries in some selected patients.

Clinical applications of intracranial pressure monitoring in traumatic brain injury : report of the Milan consensus conference.

BACKGROUND: Intracranial pressure (ICP) monitoring has been for decades a cornerstone of traumatic brain injury (TBI) management. Nevertheless, in recent years, its usefulness has been questioned in several reports. A group of neurosurgeons and neurointensivists met to openly discuss, and provide consensus on, practical applications of ICP in severe adult TBI. METHODS: A consensus conference was held in Milan on October 5, 2013, putting together neurosurgeons and intensivists with recognized expertise in treatment of TBI. Four topics have been selected and addressed in pro-con presentations: 1) ICP indications in diffuse brain injury, 2) cerebral contusions, 3) secondary decompressive craniectomy (DC), and 4) after evacuation of intracranial traumatic hematomas. The participants were asked to elaborate on the existing published evidence (without a systematic review) and their personal clinical experience. Based on the presentations and discussions of the conference, some drafts were circulated among the attendants. After remarks and further contributions were collected, a final document was approved by the participants. The group made the following recommendations: 1) in comatose TBI patients, in case of normal computed tomography (CT) scan, there is no indication for ICP monitoring; 2) ICP monitoring is indicated in comatose TBI patients with cerebral contusions in whom the interruption of sedation to check neurological status is dangerous and when the clinical examination is not completely reliable. The probe should be positioned on the side of the larger contusion; 3) ICP monitoring is generally recommended following a secondary DC in order to assess the effectiveness of DC in terms of ICP control and guide further therapy; 4) ICP monitoring after evacuation of an acute supratentorial intracranial hematoma should be considered for salvageable patients at increased risk of intracranial hypertension with particular perioperative features.

Involvement of the mitochondrial benzodiazepine receptor in traumatic brain injury: therapeutic implications.

Traumatic brain injuries represent the leading cause of death and morbidity in young adults in western countries, and are responsible for a major social and economical burden. For decades, the mainstay of neurotrauma management has been represented by control of post-traumatic edema. With the emergence of a better understanding of the underlying cellular mechanisms responsible for the generation of secondary brain damage, the hope for the "magic bullet" has prompted the development of novel drugs that have repeatedly failed to significantly improve outcome of head-injured patients. During the past decade, mitochondrial functional and structural impairment has emerged as a pivotal event in the pathway of cell to secondary death. Extensive research has identified a vast range of deleterious signals that are generated and integrated at the mitochondrial level resulting in impairment of major mitochondrial functions such as calcium homeostasis, free radicals generation and detoxification, energy production and neurosteroidogenesis. Mitochondria have therefore emerged as a potential therapeutic target. Within the spectrum of major mitochondrial structural components, the 18 kDa translocator protein (TSPO) has shown important and relevant functions such as steroid synthesis and modulation of the mitochondrial permeability transition that may substantially affect the fate of injured cells. This review summarizes the potential therapeutic implications of TSPO modulation in traumatic brain injury in the view of the current knowledge on this intriguing mitochondrial complex.

Mitochondrial targeting for development of novel drug strategies in brain injury.

For years, therapeutic approach to brain injury has been mostly physiological in essence, either based on revascularization of ischemic tissue in stroke or decompression of the swollen brain in neurotrauma. Despite tremendous efforts for the development of new strategies, translational research targeting specific cellular pathophysiological processes triggered by the injury has provided deceiving results. During the past decade, disruption of mitochondrial function and structural integrity has emerged as a pivotal event in the generation of cell damage. Following the injury, a vast array of deleterious signals are generated and integrated at the mitochondrial level resulting in impairment of three major mitochondrial functions: calcium homeostasis, free radicals generation and detoxification and energy production. Increasing understanding of the biochemical complexity of these events has led to the development of new therapeutic strategies targeting mitochondrial damage that has shown encouraging data in various models of injury. Importantly, translational efforts have been already initiated with promising preliminary data in several phase II clinical studies. In this review, we will briefly describe the process of mitochondrial damage and dysfunction following brain injury and discuss the various therapeutic strategies aiming at mitochondrial protection.

Why mortality is still high with modern care of 613 evacuated mass lesions presented as severe head injuries 1999-2009.

Of 1,949 successive acute severe head injuries (SHI) over a period of 11 years 1999-2009, 613 (31.5%) underwent evacuation of mass lesions. Mortality at 3 months of evacuated mass (EM) lesions was higher over 10 years compared with that of non-EM lesions (it was overall 22%). The reduction of mortality was significantly less in EM compared with that for non-surgical cases (14.4-9.4% recently) and for the cases that were operated but not for mass evacuation (18.1-12.1%). A few explanations are: first, more SDH (60.5% of the EM recently compared with 45.9% in the first few years); second, more severe cases and older patients with co-morbidities were treated surgically; third, advances in prehospital care brought more severe patients to operative care - the rate of referrals decreased from 61.5% to 52.8% recently; fourth, part of the significant shortening of the injury to NT admission time (163-141 min) vanished owing to the parallel elongation of admission to operation time (95-100 min), thus, the threshold recommendation of 4 h to mass evacuation was achieved in only 52%; fifth, introducing decompressive craniectomy was not associated with outcome improvement.

Comparison of effects of equiosmolar doses of mannitol and hypertonic saline on cerebral blood flow and metabolism in traumatic brain injury.

The potential superiority of hypertonic saline (HTS) over mannitol (MTL) for control of intracranial pressure (ICP) following traumatic brain injury (TBI) is still debated. Forty-seven severe TBI patients with increased ICP were prospectively recruited in two university hospitals and randomly treated with equiosmolar infusions of either MTL 20% (4 mL/kg; n=25 patients) or HTS 7.5% (2 mL/kg; n=22 patients). Serum sodium, hematocrit, ICP, arterial blood pressure, cerebral perfusion pressure (CPP), shear rate, global indices of cerebral blood flow (CBF) and metabolism were measured before, and 30 and 120 min following each infusion during the course of illness. Outcome was assessed at 6 months. Both HTS and MTL effectively and equally reduced ICP levels with subsequent elevation of CPP and CBF, although this effect was significantly stronger and of longer duration after HTS and correlated with improved rheological blood properties induced by HTS. Further, effect of HTS on ICP appeared to be more robust in patients with diffuse brain injury. In contrast, oxygen and glucose metabolic rates were left equally unaffected by both solutions. Accordingly, there was no significant difference in neurological outcome between the two groups. In conclusion, MTL was as effective as HTS in decreasing ICP in TBI patients although both solutions failed to improved cerebral metabolism. HTS showed an additional and stronger effect on cerebral perfusion of potential benefit in the presence of cerebral ischemia. Treatment selection should therefore be individually based on sodium level and cerebral hemodynamics.

The Geriatric Scoring System (GSS) in meningioma patients--validation.

BACKGROUND: Meningiomas are the most common primary brain tumor, the incidence of which rises with age. The Geriatric Scoring System (GSS) was constructed in an attempt to answer which elderly subpopulation will benefit from a surgical intervention in terms of their overall physical and functional state of health. The GSS incorporates different prognostic indicators, both clinical and radiological, for risk stratification. OBJECTIVE: The purpose of the study was to validate the previously defined GSS for the evaluation and risk stratification of elderly patients suffering from intracranial meningioma. METHODS: One hundred and twenty patients aged over 65 years admitted to the RAMBAM Medical Center with meningiomas during the years 2005-2010 were characterized, forming an independent cohort. We report the presenting symptoms, chronic illness and radiological features, as well as perioperative and long-term follow-up results up to 5 years after the surgery. RESULTS: Nine outcome parameters were tested against the GSS score on admission. Survival, Barthel Index, Karnofsky Performance Scale (KPS), consciousness expressed by the Glasgow Coma Scale (GCS) [14] score 5 years after surgery, recurrence within and beyond 12 months of surgery, the length of hospitalization both overall and in a neurosurgical intensive care unit. A GSS score higher than 16 was associated with a significantly more favorable outcome. CONCLUSION: The present results suggest that common experience-based considerations may be optimized and implemented into a simple scoring system that in turn may allow for outcome prediction and evidence-based decision making.

Improvement of cerebral metabolism mediated by Ro5-4864 is associated with relief of intracranial pressure and mitochondrial protective effect in experimental brain injury.

PURPOSE: To investigate the possible impact of reduction of mitochondrial membrane permeabilization by modulation of the 18 kDa translocator protein mediated by Ro5-4864 over post-traumatic cerebral edema and metabolic crisis. METHODS: Cerebral microdialysis and intracranial pressure (ICP) monitoring were performed in Sprague-Dawley rats treated by intraperitoneal injection of either dimethylsulfoxide (vehicle) or Ro5-4864 following cortical contusion and further correlated with quantitative assessment of mitochondrial damage, water content in the injured tissue, modified neurological severity score, and lesion size. RESULTS: Ro5-4864 resulted in a profound decrease in ICP that correlated with improved cerebral metabolism characterized by significantly higher glucose and pyruvate and lower lactate concentrations in the pericontusional area in comparison with vehicle-treated animals. Reduced ICP correlated with reduced water content in the injured tissue; improved metabolism was associated with reduced mitochondrial damage evidenced by electron microscopy. Both effects were associated with a profound and significant reduction in glycerol release and lesion size, and correlated with improved neurological recovery. CONCLUSIONS: The present study shows that Ro5-4864 has a favorable effect on the fate of injured brain, presumably mediated by improvement of metabolism. It further suggests that improvement of metabolism may contribute to ICP relief.

Maternal cerebral blood flow during normal pregnancy: a cross-sectional study.

OBJECTIVE: Pregnancy is associated with substantial changes in the maternal circulatory physiology. Our aim was to investigate maternal cerebral blood flow (CBF) during normal pregnancies. STUDY DESIGN: We prospectively measured maternal CBF in 210 low-risk pregnant women at different gestational ages, and in 15 nonpregnant women. CBF was assessed by measuring blood flow volume in the internal carotid artery (ICA) by dual-beam angle-independent digital Doppler ultrasound. RESULTS: ICA blood flow volume increased during pregnancy from 318 mL/min ± 40.6 mL/min in the first trimester to 382.1 mL/min ± 50.0 mL/min during the third trimester, corresponding to CBF values of 44.4 and 51.8 mL/min(-1)/100 g(-1), respectively (P < .0001). CBF changes were associated with progressive decrease in cerebral vascular resistance and moderate increase in ICA diameter. CONCLUSION: Maternal CBF is gradually increasing during normal pregnancy. Vasorelaxing impact of estrogens and other factors on cerebral vessels may explain the changes in CBF during pregnancy.

Moderate Ringer's lactate solution resuscitation yields best neurological outcome in controlled hemorrhagic shock combined with brain injury in rats.

Anesthetized rats were assigned to sham; brain injury (BI); controlled hemorrhagic shock (CHS); BI combined with CHS (combined injury [CI]); and CI groups resuscitated with 2.5 mL/kg Ringer's lactate solution (RL-2.5), 10 mL/kg RL (RL-10), or 40 mL/kg RL (RL-40). Brain injury was induced by applying 400 millibar negative pressure for 10 s through a hollow screw inserted into a 4.5-mm burr hole drilled into the left parietal region of the skull. Five minutes after BI, 30% of circulating blood volume was withdrawn for 10 min to induce CHS. One hour of fluid resuscitation commenced 20 min posthemorrhage. MAP, lactate, and base excess levels were significantly improved in the RL-40 group compared with all other hemorrhaged groups. The hematocrit level 1 h after resuscitation began was significantly lower in the RL-40 group (27.6% +/- 0.57%) than in all other groups. The RL-40 group had the worst neurological severity score 24 h postsurgery. MAP, lactate, and base excess levels were not significantly improved in the RL-2.5 group, however, the number of surviving neuronal cells in the perilesional brain region was significantly higher than in the CI or RL-40 groups. MAP, lactate, and base excess levels were significantly improved in the RL-10 group (P < 0.05). Mobility and the number of surviving neurons in the perilesional region of the brain were significantly better in the RL-10 group than in the CI or RL-40 groups (P < 0.05). Although massive fluid resuscitation yields preferable hemodynamic and metabolic outcomes, neurological outcomes are better after moderate fluid resuscitation for BI combined with controlled hemorrhagic shock.

Cerebral blood flow and metabolism following decompressive craniectomy for control of increased intracranial pressure.

OBJECTIVE: Decompressive craniectomy (DC) is a common practice for control of intracranial pressure (ICP) following traumatic brain injury (TBI), although the impact of this procedure on the fate of operated patients is still controversial. METHODS: Cerebral blood flow (CBF) and metabolic rates were monitored prospectively and daily as a surrogate of neuronal viability in 36 TBI patients treated by DC and compared with those of 86 nonoperated patients. DC was performed either on admission (n=29) or within 48 hours of admission (n=7). RESULTS: DC successfully controlled ICP levels and maintained CBF within a normal range although the cerebral metabolic rate of oxygen (CMRO2) was significantly lower in this group. In 7 patients, pre- and postoperative recordings showed a significant ICP decrease that correlated with CBF augmentation but not with concurrent improvement of CMRO2 that remained particularly low. Logistic regression analysis of all investigated variables showed that DC was not associated with higher mortality despite more severe injuries in this group. However, operated patients were 7-fold more likely to have poor functional outcomes than nonoperated patients. Good functional outcome was strongly associated with higher CMRO2 but not with higher CBF values. CMRO2 levels were significantly lower in the DC group, even after adjustment for injury severity, and showed a progressive and sustained trend of deterioration significantly different from that of the non-DC group. CONCLUSION: These results suggest that DC may enhance survival in the presence of severe brain swelling, although it is unlikely to represent an adequate answer to mitochondrial damage responsible for cellular energy crisis and edema.