Henry M. Bartkowski

Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination.

We have examined the incidence and size of infarction after occlusion of different portions of the rat middle cerebral artery (MCA) in order to define the reliability and predictability of this model of brain ischemia. We developed a neurologic examination and have correlated changes in neurologic status with the size and location of areas of infarction. The MCA was surgically occluded at different sites in six groups of normal rats. After 24 hr, rats were evaluated for the extent of neurologic deficits and graded as having severe, moderate, or no deficit using a new examination developed for this model. After rats were sacrificed the incidence of infarction was determined at histologic examination. In a subset of rats, the size of the area of infarction was measured as a percent of the area of a standard coronal section. Focal (1-2 mm) occlusion of the MCA at its origin, at the olfactory tract, or lateral to the inferior cerebral vein produced infarction in 13%, 67%, and 0% of rats, respectively (N = 38) and produced variable neurologic deficits. However, more extensive (3 or 6 mm) occlusion of the MCA beginning proximal to the olfactory tract--thus isolating lenticulostriate end-arteries from the proximal and distal supply--produced infarctions of uniform size, location, and with severe neurologic deficit (Grade 2) in 100% of rats (N = 17). Neurologic deficit correlated significantly with the size of the infarcted area (Grade 2, N = 17, 28 +/- 5% infarction; Grade 1, N = 5, 19 +/- 5%; Grade 0, N = 3, 10 +/- 2%; p less than 0.05). We have characterized precise anatomical sites of the MCA that when surgically occluded reliably produce uniform cerebral infarction in rats, and have developed a neurologic grading system that can be used to evaluate the effects of cerebral ischemia rapidly and accurately. The model will be useful for experimental assessment of new therapies for irreversible cerebral ischemia.

Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats.

We have evaluated the use of 2,3,5-triphenyltetrazolium chloride (TTC) as an histopathologic stain for identification of infarcted rat brain tissue. The middle cerebral artery (MCA) of 35 normal adult rats was occluded surgically. At various times after surgical occlusion, rats were sacrificed and brain slices were obtained and stained with TTC or hematoxolin and eosin (H & E); the size of the area of infarcted tissue stained by each method was quantified. In rats sacrificed 24 hr after occlusion of the MCA, the size of the area of infarction was 21 +/- 2% of the coronal section for TTC, and 21 +/- 2% for H & E (mean +/- S.D., N = 13). The size of areas of infarction determined by either staining method was not significantly different in area by the paired test, and a significant correlation between sizes determined by each method was found by linear regression analysis (r = 0.91, slope = 0.89, and the y intercept = 4.4%). Staining with TTC is a rapid, convenient, inexpensive, and reliable method for the detection and quantification of cerebral infarction in rats 24 hr after the onset of ischemia.

Postconcussive symptoms in children with mild closed head injuries.

OBJECTIVE To examine the incidence and neuropsychological, behavioral, and neuroimaging correlates of postconcussive symptoms (PCS) in children with mild closed head injuries (CHI). DESIGN 26 Children with mild CHI and 8 of their uninjured siblings, from 8 to 15 years old, were recruited prospectively and assessed at baseline (ie, within 7 days of injury) and at 3 months postinjury. Parents rated PCS, motivation and affective lability, and behavioral adjustment. Baseline ratings assessed premorbid functioning retrospectively, and follow-up ratings assessed postinjury status. On both occasions, children completed neuropsychological testing, and those with mild CHI also underwent magnetic resonance imaging (MRI). RESULTS Children with mild CHI did not differ from siblings in baseline ratings of premorbid PCS but displayed higher ratings on several PCS at 3 months postinjury. Thirty-five percent of children with mild CHI showed increases in PCS, compared with baseline premorbid ratings, but none of the siblings did so. Children with mild CHI whose PCS increased from premorbid levels showed poorer neuropsychological functioning at baseline than did children whose PCS did not increase, although the differences had partially resolved by 3 months. They also displayed decreased motivation over time. Their behavioral adjustment was poorer and they had smaller white matter volumes on MRI, but the latter differences were present at baseline and did not change over time, suggesting that they existed prior to the injury. CONCLUSION Postinjury increases in PCS occur in a sizable minority of children with mild CHI and more often than among uninjured siblings. Increases in PCS following mild CHI are associated with premorbid neurological and psychosocial vulnerability, but also with postinjury decrements in neuropsychological and neurobehavioral functioning.

Effect of hypoxia on traumatic brain injury in rats: Part 1. Changes in neurological function, electroencephalograms, and histopathology.

The effect of hypoxia on neurological function, compressed spectral array electroencephalography, and histopathology in head-injured rats was evaluated. By itself, an hypoxic insult (PaO2, 40 mm Hg for 30 minutes) caused no neurological deficit. Twenty per cent of rats injured by a 5-atmosphere temporal fluid percussion impact were hemiparetic contralateral to the side of impact, whereas 80% had no deficit 24 hours after injury. Seventy per cent of rats with both fluid impact injury and hypoxic insult, however, either had a definite hemiparesis, showed no spontaneous movement, or died (P less than 0.02). Impact alone produced an initial depression in electroencephalogram power that was prolonged in rats with hypoxic insult; the most dramatic effect was found in the injured hemisphere, with shorter and less profound effects in the contralateral hemisphere. Perfusion staining of injured cerebral tissue in vivo with 2,3,5-triphenyltetrazolium chloride showed an area of extensive ischemia around the impact site in rats with hypoxic insult. This ischemic area was not present in rats with either impact injury or hypoxia alone. We conclude that posttraumatic hypoxia clearly increases the severity of impact injury in this rat model. These findings suggest that hypoxia, which is common in head-injured patients, very likely worsens the effect of impact injury and may account for much of the diffuse neurological dysfunction in patients with severe craniocerebral trauma.

Traumatic intracerebral hematomas: timing of appearance and indications for operative removal.

Immediate and delayed traumatic intracerebral hematomas (ICH) can produce devastating secondary brain damage after severe head injury. The relationship between the initial injury and eventual occurrence, size, and time of appearance of such hematomas is not well understood, but has great importance since delayed appearance may necessitate delayed surgical decompression of developing lesions not present on early CT scans. We reviewed the records of 35 consecutive patients with operated post-traumatic ICH to document when these lesions appeared on CT, what were the indications for surgery, and what was eventual outcome. Time between injury and ICH appearance was categorized as immediate (0-3 hours), intermediate (3-6), delayed (6-24) or very delayed (later than 24 hours). ICH appearance was immediate in 20%, intermediate in 6%, delayed in 29%, and very delayed in 46%. Half of the patients were not comatose at the time of admission (GCS greater than or equal to 8). Hematoma removal was prompted by clinical deterioration or failure to improve in half the patients and by uncontrolled intracranial hypertension in the other half. Half the patients died, generally those in traumatic coma immediately after injury although advanced age also was associated with poor outcome. Only about one quarter of patients who require surgical removal of ICH can be shown to have their lesions soon after injury. Most operable intraparenchymal clots develop after initial CT scanning and trauma surgeons must be prepared to recognize and treat this delayed complication of brain injury. Even with aggressive management, ICH contribute significantly to poor outcome and improved treatment must be sought.

Effect of hypoxia on traumatic brain injury in rats: Part 2. Changes in high energy phosphate metabolism.

The effect of different degrees of hypoxia on phosphate metabolism in the brains of impact-injured rats was studied using in vivo phosphorus-31 magnetic resonance (P-31 MR) spectroscopy. Sequential changes in P-31 MR spectra within 60 minutes of insult were compared among rats with hypoxia alone, impact injury alone, or a combined impact-hypoxic insult. Hypoxia alone (PaO2 of 40 mm Hg for 30 minutes) caused no remarkable changes in phosphorus spectra except a decrease in intracellular pH. In impact-injured rats, the concentration of inorganic phosphate (Pi) increased, but signals for phosphocreatine (PCr) and beta-adenosine triphosphate (beta-ATP) did not change, and the ratio of PCr/Pi changed only slightly to 7% below control value. When rats with a fluid percussion impact injury of 5 atm were subjected to hypoxic conditions of a PaO2 of 40 mm Hg for 15 minutes, the PCr/Pi ratio decreased by 14%, a value significantly below that of the impact alone group (P less than 0.05). After longer periods of hypoxia (PaO2 of 40 mm Hg for 30 minutes) in impact-injured rats, there were marked increases of Pi and significant decreases in signals for PCr and beta-ATP, which caused a marked decrease in the PCr/Pi ratio to 39% below control values (P less than 0.001). Milder hypoxia (PaO2 of 50 mm Hg for 30 minutes) plus impact injury caused smaller changes in high energy metabolite concentrations, and the PCr/Pi ratio decreased to 15% below control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Is Computed Tomographic Scanning Necessary in Patients with Tentorial Herniation?Results of Immediate Surgical Exploration without Computed Tomography in 100 Patients

Computed tomographic (CT) scans are performed on virtually all patients with severe head injury at the time of admission. Because of the time involved in obtaining these studies, the evacuation of significant intracranial mass lesions is delayed. To avoid such delays, the authors performed burr-hole exploration for the diagnosis of intracranial hematomas before CT scans were obtained in 100 consecutive head-injured patients with clinical signs of tentorial herniation or upper brain stem dysfunction upon admission to the emergency room. Patients in whom a hematoma was discovered had a craniotomy for evacuation of the clot; those in whom the exploration was negative had a CT brain scan immediately after operation. Burr-hole exploration revealed extracerebral mass lesions in 56 patients. In 38 patients, the exploration was negative, and postoperative CT scanning showed no significant hematoma. Of 6 patients in whom the CT scan demonstrated extraaxial hematomas requiring surgical evacuation, 4 had subdural hematomas that were missed because the exploration was incomplete; 1 patient had an epidural hematoma and 1 had a subdural hematoma contralateral to a craniotomy on the side of a positive initial burr-hole exploration. Our results indicate that the relatively small subgroup of head-injured patients with early tentorial herniation or upper brain stem compression have a high incidence of immediate extraaxial hematomas and a low incidence of intracerebral hematomas. This is particularly true of patients over 30 years of age and those who suffer low speed trauma, such as falls and vehicle-pedestrian accidents.

Proton nuclear magnetic resonance spectroscopy of normal and edematous brain tissue in vitro: Changes in relaxation during tissue storage

Proton nuclear magnetic resonance relaxation times, T1 and T2, of water in unfixed gray and white matter from normal and edematous rabbit brain tissues were measured in vitro at 23 degrees C and 100 MHz to evaluate the effects of the temperature (-25 degrees C to 37 degrees C) and duration (0 to 96 h) of tissue storage on relaxation times. T1 and T2 tended to decrease during storage, probably from slow dehydration of the tissue. This effect was greatest in tissues stored at 37 degrees C and least in those stored at 4 and -25 degrees C; decreases in T1 and T2 were greater in white matter than in gray matter. Freezing brain tissue to -25 degrees C caused a sudden decrease in the T2 of normal white matter. Relaxation times were constant for 5 h in tissues stored at 23 degrees C and for 40 h at 4 degrees C. These results correlated well with corresponding tissue water loss.

NMR imaging and spectroscopy of experimental brain edema.

A canine model of experimental brain edema utilizing the classic cold lesion technique was used to identify the optimal nuclear magnetic resonance (NMR) spin-echo imaging parameters needed to detect cerebral edema with maximum sensitivity. Each animal was studied with four separate spin-echo sequences, utilizing pulse intervals ranging from 0.5 to 2.0 seconds. The echo delays following each pulse interval were 28 and 56 msec. Cerebral edema was best identified with the longest pulse interval (2.0 seconds), and the second echo delay (56 msec). T1 and T2 relaxation values were obtained from in vitro spectroscopy. The relaxation times were prolonged in the edematous white matter; however, absolute T1 and T2 values proved of little use in comparing different animals.

The Effect of Dimethylsulfoxide (DMSO) on Intracranial Pressure and Outcome After Severe Head Injury

Despite aggressive surgical and intensive medical management of patients with severe head injury, uncontrolled ICP elevation still occurs with disappointing regularity and frequently is associated with death or severe disability. Anecdotal reports have suggested that elevated ICP in traumatic coma, unresponsive to induced barbiturate coma and other standard management regimens, can be lowered by intravenous administration of DMSO (Waller 1983; Marshall 1984). In an attempt to improve management of traumatic intracranial hypertension, we have conducted a prospective randomized controlled trial of DMSO compared to conventional therapy to assess its effects on ICP and outcome after severe head injury.