Biomedical subjects

L H Pitts

Publications and source records attributed to L H Pitts.

At least 19 recordsLinked to original sources

PubMed1996

Intervertebral disc space infection caused by Aspergillus fumigatus.

The authors describe the case of a 53-year-old woman who suffered from an Aspergillus fumigatus infection of the L2/3 intervertebral disc space unrelated to previous operations on her lumbar spine. After surgical debridement combined with amphotericin therapy she died on the 23rd postoperative day from a fulminant bacterial sepsis of pulmonary origin. Although she had intermittently used steroids for bronchial asthma, this is an unusual case of fungal infection of the lumbar spine in an apparently immunocompetent patient.

Amphotericin B↗

PubMed1996

Purkinje cell vulnerability to mild traumatic brain injury.

In this study we examined the cerebellar response to mild traumatic brain injury by assessing microglial activation and Purkinje cell loss. Activated microglia were identified using the antibodies OX-42 and ED-1 as well as isolectin B4. The anti-Purkinje cell antibody PEP-19 was used to evaluate Purkinje cell loss after injury. The mechanism of cell injury was examined using a monoclonal antibody to the inducible 72-kDa heat shock protein. A monoclonal antibody to the N-terminal sequence of Fos was used as a marker for neuronal activation. There was progressive activation of microglia in the cerebellar vermis within a few days after forebrain injury. In coronal sections the processes of activated microglia were oriented in "stripes" perpendicular to the cortical surface. In sagittal sections the activated microglia were in irregularly shaped clusters or in a fan-like distribution that radiated from the Purkinje cell layer toward the cortical surface. There was a significant loss of Purkinje cells 7 days postinjury as compared to the control group. There was no evidence of induction of heat shock protein in the cerebellum. In addition, there was no evidence of induction of c-Fos protein in either the cerebellar cortex or inferior olivary nuclei within the first 3 h after injury. These studies demonstrate that a fluid percussive impact to the forebrain results in cerebellar damage. The close anatomical association between activated microglia and Purkinje cells suggests that Purkinje cell injury is the cause of the microglial activation. The mechanism of Purkinje cell death, however, remains unclear.

Animals↗

PubMed1996

Predicting survival from head trauma 24 hours after injury: a practical method with therapeutic implications.

OBJECTIVE: To develop a method to predict long-term outcome after head injury and determine if outcome can be accurately predicted 24 hours after injury. DESIGN: A retrospective review was performed on a study cohort of 672 head-injured patients admitted in coma (Glascow Coma Scale score < or = 8) who remained comatose for at least 6 hours, survived more than 24 hours, and had 6-month outcome data available. Stepwise logistic regression analysis was used to determine which clinical variables predicted 6-month outcome. Statistically significant clinical predictors were combined into a single examination variable (MPX score), which reflected a rank-ordering of examinations from worst to best, which was then further weighted by patient age. The relation between 6-month outcome and MPX score at admission and 24 hours was plotted and analyzed. MEASUREMENT AND MAIN RESULTS: Age, best motor score, and pupillary reactivity at admission and 24 hours were significant predictors of outcome; extraocular motility was predictive at 24 hours only. Age was the most important independent predictor, followed by best motor score, pupillary reactivity, and extraocular motility. Combining these predictors into MPX score resulted in a set of graphs that reliably predicted long-term outcome. The 24-hour MPX data were better predictors of 6-month outcome and were more specific in predicting negative outcomes than admission data. CONCLUSIONS: The method is simple to use, relying on bedside neurologic examination and a single graph, but appears to predict long-term outcome accurately as early as 24 hours after head injury. If validated on other large series of patients, this method could provide an objective and practical basis for terminating care in patients unlikely to survive a head injury.

Adolescent↗

PubMed1995

Treatment with thyrotropin-releasing hormone (TRH) in patients with traumatic spinal cord injuries.

Numerous preclinical studies have demonstrated that posttraumatic treatment of spinal cord injury (SCI) with thyrotropin-releasing hormone (TRH) or TRH analogs improves long-term behavioral recovery. The purpose of the present study is to provide preliminary data regarding the safety and potential efficacy of TRH in patients with acute SCI. A total of 20 patients with SCI were classified by clinical examination into complete and incomplete injury groups within 12 h of trauma and randomly assigned in double-blinded fashion to treatment with either TRH (0.2 mg/kg intravenous bolus followed by 0.2 mg/kg/h infusion over 6 h) or vehicle (equal volume physiological saline) placebo. A variety of physiological variables were followed during treatment. Clinical examination included motor and sensory testing, as well as assigning a Sunnybrook score based upon level of function. Patients were examined at 24 h, 72 h, 1 week, 1 month, 4 months, and 12 months after injury. TRH infusions were well tolerated. There appeared to be no discernible treatment effect in patients with complete injuries although data were available from only six such patients at 4 months. For the incomplete injury group, a total of 6 treated and 5 placebo patients had 4-month evaluations. TRH treatment was associated with significantly higher motor, sensory, and Sunnybrook scores than placebo treatment. Because of patients lost to subsequent follow-up, 12-month data were not highly informative. These observations must be interpreted with considerable caution because of the small patient numbers, but together with extensive animal studies they support the need for a larger multicenter clinical trial of TRH.

Adult↗

PubMed1995

Altered immunoexpression of microglia and macrophages after mild head injury.

In this study we examined the temporal response of microglia and macrophages to mild head injury in the rat. Microglia and macrophages were identified by their distinct morphology and by immunophenotype. With regard to the latter, antibodies to OX42 and ED1 were used to define microglia and macrophages, respectively. Although there was no change in the morphology of brain macrophages after mild head injury, the morphology of microglia was dramatically altered. Microglial cell bodies appeared larger with a more elaborate arborization of cellular processes. After head injury certain populations of macrophages and microglia were more intensely immunostained. By 3 days postinjury these intensely stained cells exhibited a characteristic distribution in the brain. Prominently stained microglia were detected in the thalamus, hippocampus, lateral and medial geniculate body, and the substantia nigra. Intensely stained macrophages were located primarily in the cortex and subarachnoid space adjacent to the site of impact. By 7 days postinjury intensely immunostained macrophages and microglia were widespread throughout the injured cortex. These results demonstrate that microglia and macrophages are sensitive to mild head injury. Early changes in the macrophage population are more directly correlated with the most damaged tissue and may reflect migration of these cells from either the subarachnoid space or across the damaged blood-brain barrier. The early widespread microglial response in regions exhibiting no overt neuronal cell damage suggests that these cells are responding to more subtle factor(s) that are expressed in the mildly traumatized brain.

Animals↗

PubMed1995

Withholding and withdrawing of life support from patients with severe head injury.

OBJECTIVE: To characterize the withholding or withdrawing of life support from patients with severe head injury. SETTING: San Francisco General Hospital, a city and county hospital with a Level I trauma center. DESIGN: A standardized questionnaire was used to collect data on demographics and functional outcome of severely head-injured (Glasgow Coma Score of < or = 7) patients admitted to the medical-surgical intensive care unit, and to interview the patients' physician and family members. PATIENTS: Forty-seven patients who were admitted to a medical-surgical intensive care unit over a 1-yr period. INTERVENTIONS: Twenty-four patients had life support withheld or withdrawn, and 23 patients did not. MEASUREMENTS AND MAIN RESULTS: Physician and family separately assessed patient's probable functional outcome, degree of communication between them, reasons important in recommending or deciding on discontinuation of life support, and the result of action taken. Six months later, the families reviewed the process of their decision, how well physician(s) had communicated, and what might have improved communication. Of 24 patients with life support discontinued, 22 died; two were discharged from the hospital. Twenty-three of the 24 patients had a poor prognosis on admission. Of the 23 patients who were continued on life support for the duration of their hospitalization, ten had a poor (p < .001) prognosis on admission. Prognosis improved for two patients from the first group and five from the latter. Family's assessment of prognosis agreed with physician's assessment in 22 of the 24 patients from whom life support was discontinued (p < .001). Physicians' ability to convey the prognosis appeared to influence families' assessments. Physicians' considerations in recommending limitation of care and families' considerations in making decisions were the same, primarily an inevitably poor prognosis. Neither physician nor families cited cost or availability of care as a deciding factor. Two families disagreed with the recommendation to limit care after initial agreement because the patients' prognosis improved from "likely death" to "vegetative." Care was therefore continued, and both patients remained vegetative 6 months after admission to the hospital and discharge to chronic care facilities. CONCLUSIONS: Life support is commonly withheld or withdrawn from patients with severe head injury at San Francisco General Hospital, and usually it is accompanied by death. A reciprocal consideration exists in most cases between the physician and family making the difficult decision to limit care. Care is provided for patients whose families request it despite physician recommendations.

Adolescent↗

PubMed1995

Neurotrauma and trauma systems.

Optimal trauma care, including that for head and spinal cord injury, requires system organization and adoption throughout the United States and the world. Neurosurgeons play an essential role in system design and development in addition to treating neurotrauma patients. Areas of neurosurgical involvement include defining prehospital triage and treatment guidelines, emergency department evaluation and therapy, operative management, and active involvement in the critical care and acute hospital settings. Collaboration among all members of the trauma team is essential to ensure the best possible outcome for patients with traumatic injuries.

Brain Injuries↗

PubMed1995

Interconnecting the posterior and middle cranial fossae for tumors that traverse Meckel's cave.

Meckel's cave is an avenue for tumor to spread between the posterior and middle cranial fossae. The most common neoplasms that traverse this channel are trigeminal schwannomas and meningiomas. The classic approach to address disease in both cranial fossae involves separate craniotomies. Recent innovations in skull base surgery have made it possible to perform a single opening with simultaneous exposure of the posterior and middle fossae, without undue brain retraction. Tumors with a large middle fossa component and a smaller posterior fossa portion are exposed via subtemporal craniotomy with petrosectomy and tentorium division. However, tumors with a large posterior fossa component and a smaller middle fossa portion in the setting of serviceable hearing are addressed with retrosigmoid craniotomy and petrosectomy. For bilobed tumors with substantial components in both fossae, subtemporal craniotomy combined with varying degrees of transtemporal petrosectomy and tentorium division is employed. The evolution of techniques to address tumors that traverse Meckel's cave is reviewed and a treatment algorithm is proposed.

Brain Neoplasms↗

PubMed1995

Delayed onset facial nerve dysfunction following acoustic neuroma surgery.

Delayed onset facial nerve dysfunction following acoustic neuroma surgery is an under-appreciated phenomenon. The authors have recently reviewed long-term (> 1 year) facial nerve outcome in 129 patients who underwent acoustic neuroma removal with the aid of cranial nerve monitoring between 1986 and 1990. The facial nerve was anatomically preserved in 99.2% of the patients, and at one year, 90% of all the patients had House-Brackmann (H-B) grade I or II facial nerve function. Delayed onset worsening of facial nerve function was noted in 38 of 129 (29%) patients, most of which occurred in the first few postoperative days. The incidence increases to 41% (38 of 93) when corrected for those with immediate H-B grade VI weakness, and who therefore could not manifest further deterioration. The facial nerve function either deteriorated from normal to abnormal or increased in severity of weakness. Delayed facial palsy was not related to the size of tumor or the surgical approach. The most common occurrence was that of a patient with H-B grade I or II facial nerve function worsening to H-B grade VI in the postoperative period. The prognosis for recovery of facial nerve function following delayed palsy was excellent. In the majority of cases, the recovery was complete within the first 6 months without specific treatment. Comparable to the patients without delayed palsies, 89% (34 of 38) of the cases had H-B grade I or II and 97% (37 of 38) had H-B grade III or better facial nerve function at 1 year. This review suggests a surprisingly high incidence of delayed facial palsy following acoustic neuroma surgery, which fortunately has an excellent prognosis for spontaneous recovery.

Adult↗

PubMed1995

Systematic approach to intradural tumors ventral to the brain stem.

Intradural tumors that are situated anterior to the midbrain, pons, and medulla have historically been among the most inaccessible of all intracranial lesions. The classic approaches to the posterior fossa (e.g., suboccipital, retrosigmoid) provide only limited access to the anterior midline, primarily due to interposition of the cerebellum, brain stem, and numerous cranial nerves between the tumor and the viewpoint of the surgeon. A variety of techniques have been developed in recent years that create a craniotomy by removal of a portion of the lateral skull base. These procedures enhance exposure of the ventral surface of the brain stem while markedly reducing the need for brain retraction. An underlying theme of transbasal craniotomy is judicious removal of a portion of the petrous pyramid. The most radical form of petrosectomy, the extended transcochlear approach, involves removal of the entire petrous pyramid along with the lateral aspect of the clivus. This provides an unimpeded view of the ventral surface of the pons, including the basilar artery, vertebrobasilar junction, and both abducens nerves. Whereas this technique provides splendid exposure along the midsegment of the brain stem, it carries substantial morbidity, including hearing loss and transient facial palsy, which typically recovers incompletely and with synkinesis. Over the past few years transcochlear procedures have been gradually supplanted, at the University of California Medical Center, by techniques that involve creating a simultaneous craniotomy of both the middle and posterior fossae fashioned around a more limited petrosectomy. These versatile procedures, in particular the middle fossa/retrolabyrinthine approach, provide excellent exposure of the region ventral to the midbrain and pons with less morbidity than the transcochlear approach. When tumors extend inferiorly, ventral to the lower medulla and/or upper cervical spinal cord, augmented inferior exposure is required. Approaches to ventrally situated lesions at the craniovertebral junction include the far lateral (transcondylar) approach to the foramen magnum and the transjugular approach, both of which involve removal of the inferior portion of the petrous bone. To efficiently utilize these innovative surgical options the surgeon must decide which of the potential approaches optimizes resection while minimizing morbidity. An analysis of the anatomy of the tumor, the functional integrity of cranial nerves, and the extent of resection planned provides the surgeon with the information needed to arrive at a rational choice.

Brain↗

PubMed1994

Fluid-phase endocytosis of horseradish peroxidase by cerebral endothelial cells in primary culture: characterization and kinetic analysis.

Endocytosis of horseradish peroxidase (HRP) was studied in primary cultures of cerebral endothelial cells prepared from 2-week-old rats. These cultures were considered "endothelial-like" on the basis of their ability to internalize acetylated low density lipoprotein. Cellular localization of HRP protein was examined at the light and ultrastructural levels and endocytosis of the protein was evaluated by a colorimetric assay. HRP was localized in discrete cytoplasmic granules by light microscopy. At the ultrastructural level these granules corresponded to pleomorphic membrane-bound structures that were present throughout the cytoplasm. The amount of internalized HRP was directly related to the concentration of the protein in the medium, was not saturable at high concentrations of HRP, and increased with time. Endocytosis proceeded at 37 degrees C, but was abolished at 4 degrees C. In pulse-chase experiments, the quantity of internalized protein in the cells did not significantly change during the 2 hr chase period. Taken together, these findings suggest that internalization of HRP occurs by fluid-phase endocytosis, a non-receptor-mediated process, and that the protein is stable within an intracellular compartment for at least several hours.

Animals↗

PubMed1994

Immunocytochemical localization of immunoglobulins in the rat brain: relationship to the blood-brain barrier.

The central nervous system has been traditionally regarded as an immunologically privileged area. This feature has been in part attributed to the blood-brain barrier, which provides a restrictive interface to circulating immunoglobulins (IgG). Recent kinetic studies suggest that the barrier to immune proteins is not absolute, but rather may be regulated by a specific transfer mechanism. In this study, we confirm the presence of IgG in the central nervous system by immunocytochemistry and demonstrate a close anatomical relationship between the distribution of this protein and the blood-brain barrier. IgG was immunolocalized in the normal rat brain by using monoclonal and polyclonal antibodies to IgG and its subclasses. On the basis of an initial evaluation, the most appropriate antibodies and dilutions were selected for subsequent analyses. In the first study, IgG and albumin were immunolocalized in adjacent sections. In the second study, horseradish peroxidase (HRP) was given intravenously prior to sacrifice, in order to examine artifacts related to perfusion fixation. The distribution of HRP and IgG was then examined in adjacent sections. In the third study, IgG was immunolocalized in sections of brain after mild traumatic head injury. A monoclonal antibody to IgG2a and a polyclonal antibody to IgG were selected on the basis of specificity and consistent, mutual localization. Distinct, patchy, perivascular staining, infrequently associated with labeled neurons, was noted throughout the brain. Electron microscopy confirmed the perivascular localization; IgG was localized along the basal lamina of microvasculature and within the adjacent parenchyma. Albumin and HRP did not exhibit a similar pattern of perivascular immunostaining. After head injury, prominent immunostaining for IgG was observed in the injured hemisphere. In summary, these data indicate that the normal rat brain contains IgG, which dramatically increases after head injury. The distinct perivascular distribution in the normal brain suggests local microvascular permeability. This permeability is selective for IgG, since albumin does not share a similar perivascular localization. The neuronal staining which is closely associated with perivascular label may reflect one intracellular route for extravasated IgG.

Albumins↗

PubMed1994

Facial nerve outcome after acoustic neuroma surgery: a study from the era of cranial nerve monitoring.

The introduction of intraoperative cranial nerve monitoring in posterior fossa surgery has greatly aided the surgeon in identification and anatomic preservation of cranial nerves. As a result, the long-term function of the facial nerve continues to improve after removal of acoustic neuroma. Herein, we report our long-term (1 year or greater) facial nerve outcome in 129 patients who underwent surgical removal of their acoustic neuromas with the aid of intraoperative neurophysiologic monitoring between 1986 and 1990. The facial nerve was anatomically preserved in 99.2% of the patients, and 90% of all the patients had grade 1 or 2 facial nerve function 1 year after surgery. Long-term facial function was inversely correlated with the size of tumor (chi-squared, p < 0.02) and was not related to the side of tumor, the age and sex of the patient, or the surgical approach. In a comparison among tumor groups matched for size, no statistically significant difference in facial nerve outcome between the translabyrinthine and retrosigmoid approaches was detected. The proximal facial nerve stimulation threshold at the end of surgical removal was predictive of long-term facial nerve function (analysis of variance, p < 0.02). At 1 year, 98% (87 of 89) of the patients with electrical thresholds of 0.2 V or less had grade 1 or 2 facial nerve function compared with only 50% (8 of 16) of those with thresholds between 0.21 and 0.6 V. In the era of cranial nerve monitoring, patients can be better advised about long-term facial nerve outcome after surgical intervention. Preoperatively, the size of the tumor is the most critical factor in predicting long-term facial function. Postoperatively, the proximal seventh nerve stimulation threshold at the end of the surgical procedure can be used as one prognostic measure of long-term facial nerve function.

Adult↗

PubMed1993

Immunolocalization of heat shock protein after fluid percussive brain injury and relationship to breakdown of the blood-brain barrier.

We have previously developed a model of mild, lateral fluid percussive head injury in the rat and demonstrated that although this injury produced minimal hemorrhage, breakdown of the blood-brain barrier was a prominent feature. The relationship between posttraumatic blood-brain barrier disruption and cellular injury is unclear. In the present study we examined the distribution and time course of expression of the stress protein HSP72 after brain injury and compared these findings with the known pattern of breakdown of the blood-brain barrier after a similar injury. Rats were subjected to a lateral fluid percussive brain injury (4.8-5.2 atm, 20 ms) and killed at 1, 3, and 6 h and 1, 3, and 7 days after injury. HSP72-like immunoreactivity was evaluated in sections of brain at the light-microscopic level. The earliest expression of HSP72 occurred at 3 h postinjury and was restricted to neurons and glia in the cortex surrounding a necrotic area at the impact site. By 6 h, light immunostaining was also noted in the pia-arachnoid adjacent to the impact site and in certain blood vessels that coursed through the area of necrosis. Maximal immunostaining was observed by 24 h postinjury, and was primarily associated with the cortex immediately adjacent to the region of necrosis at the impact site. This region consisted of darkly immunostained neurons, glia, and blood vessels. Immunostaining within the region of necrosis was restricted to blood vessels. HSP72-like immunoreactivity was also noted in a limited number of neurons and glia in other brain regions, including the parasagittal cortex, deep cortical layer VI, and CA3 in the posterior hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of U74006F on neurologic function and brain edema after fluid percussion injury in rats.

The effect of the 21-aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, on neurologic outcome and cerebral edema was evaluated in adult male Sprague-Dawley rats subjected to a fluid percussion temporal brain injury followed by 45 min of hypoxia (PaO2 = 30.0 mm Hg). The rats were divided randomly into five groups. Bolus injections of a control drug or U74006F (1.0, 3.0, 10.0, or 30.0 mg/kg) were given 3 min and 3 h after the injury. Twenty-four hours after the injury, the neurologic status was evaluated, the rats were killed, and brain water content was determined by microgravimetry. U74006F did not significantly reduce brain water content at any dose level, nor did it affect rotorod walking or activity scores. However, rats treated with U74006F at a dose of 10.0 mg/kg had significantly better motor function scores (p < 0.05) than rats in the control group. These findings demonstrate the usefulness of U74006F as a cerebroprotective agent in this model of experimental head injury.

Animals↗

PubMed1993

Isolated metastatic melanoma of the cerebellopontine angle: case report.

Malignant melanoma is a common cause of central nervous system metastases. This report describes an extremely rare case of metastatic melanoma presenting as an isolated cerebellopontine angle tumor. Clinically and radiographically, the lesion mimicked an acoustic neuroma. The patient had neuro-otological symptoms, including tinnitus, vertigo, sensorineural hearing loss, facial nerve dysfunction, and prominent cerebellar dysfunction. Magnetic resonance images showed a lesion of the internal auditory canal and cerebellopontine angle that was hypointense on T1-weighted images, hyperintense on T2-weighted images, and enhanced after the administration of gadolinium. T2-weighted images showed significant cerebellar edema. Subtotal resection of the tumor through a suboccipital craniotomy palliated the symptoms, but the patient died of tumor progression 6 months later. In contrast to other metastatic tumors of the temporal bone, melanoma initially metastasizes to the internal auditory canal and is characterized by early neurovascular infiltration. This report highlights the pathophysiological characteristics, radiological findings, differential diagnosis, and treatment of metastatic melanoma of the internal auditory canal and cerebellopontine angle.

Adult↗

PubMed1992

Breakdown of the blood-brain barrier after fluid percussive brain injury in the rat. Part 1: Distribution and time course of protein extravasation.

Experimental brain injury is associated with marked vasogenic edema, as evidenced by an increase in brain water content. This prominent and widespread response raises questions about the vulnerability of microvasculature in the brain to injury. In the present report we further characterize the vascular response by evaluating the integrity of the blood-brain barrier to circulating proteins. Vascular permeability to endogenous immunoglobulins (IgG) and to the protein horseradish peroxidase (HRP) was examined after a lateral, fluid percussive brain injury in the rat. In study 1 IgG was immunolocalized in brain sections 1-24 hr after injury. In studies 2 and 3 HRP was given intravenously either before impact (study 2) or 10 min before sacrifice (study 3). Permeability to this protein was assessed at 1-6 hr (study 2) or at 1-72 hr (study 3) after injury. In studies 1 and 2 the extravascular accumulation of proteins was evaluated. Pronounced abnormal permeability to IgG and HRP occurred within the first hour after injury and was widespread throughout both hemispheres. The intensity of immunostaining for IgG increased with time up to 24 hr after injury. In contrast, maximal extravascular accumulation of HRP occurred within the first hour after injury. In study 3 the time course for re-establishment of the blood-brain barrier to HRP was determined. Maximal permeability occurred at 1 hr after injury. At 24 hr abnormal permeability was restricted to the impact site and this area remained permeable up to 72 hr after injury. In summary this study demonstrates that breakdown of the blood-brain barrier to plasma proteins is a prominent feature of experimental brain injury. This abnormal permeability is characterized by its transient expression and widespread distribution. The time course for re-establishment of the blood-brain barrier to circulating proteins is most delayed at the impact site.

Animals↗

PubMed1992

Breakdown of the blood-brain barrier after fluid percussion brain injury in the rat: Part 2: Effect of hypoxia on permeability to plasma proteins.

Clinical studies have demonstrated that hypoxia after severe brain injury is common and significantly worsens neurologic outcome. We have, therefore, developed a rat model of posttraumatic hypoxic injury in order to identify the pathophysiologic responses after head injury that are worsened by this secondary insult. We examined the effect of hypoxia after brain injury on permeability of the blood-brain barrier to plasma proteins. Animals were divided into two experimental groups: group I (impact alone) and group IH (impact plus hypoxia). Rats were subjected to a lateral fluid percussive brain injury (4.8-5.2 atm). Animals in group IH were exposed to hypoxic conditions (10% O2) for 45 min immediately after injury. In each group, vascular permeability to endogenous immunoglobulins (IgG) and to horseradish peroxidase (HRP) was examined at the light microscopic level. IgG was immunolocalized in brain sections at 1-24 h after injury. In other studies, HRP was given i.v. either before impact or 10 min before killing. Permeability to this protein was assessed at 1-72 h after injury. The distribution of extravasated proteins was similar between the experimental groups at 1 h postinjury. Pronounced abnormal permeability to IgG and HRP (given before impact) occurred in discrete regions throughout both the ipsilateral and contralateral hemispheres. By 6 h after injury, a differential response of the blood-brain barrier was noted between groups I and IH. Widespread leakage of proteins was observed in the injured hemisphere in group IH. This finding was in sharp contrast to group I, in which extravasated proteins remained more localized in the injured hemisphere. The time course for reestablishment of the blood-brain barrier to HRP (given before killing) was determined. The impact site remained permeable to HRP up to at least 72 h postinjury within groups I and IH. In group I, the blood-brain barrier was reestablished in the parasagittal cortex and deep cortical layer by 6 h postinjury. In contrast, the blood-brain barrier in group IH was not restored in similar brain regions until 24 h postinjury. These studies demonstrate that (1) hypoxia after brain injury exacerbates the regional breakdown of the blood-brain barrier to circulating proteins, (2) this influence of hypoxia on permeability is not apparent immediately after injury but rather is expressed at 6 h after injury, and (3) hypoxia after traumatic brain injury delays recovery of the blood-brain barrier. These findings suggest that secondary posttraumatic hypoxia contributes to the vascular pathogenesis of brain injury.

Animals↗