Early metabolic alterations in edematous perihematomal brain regions following experimental intracerebral hemorrhage.

OBJECT: The authors previously demonstrated, in a large-animal intracerebral hemorrhage (ICH) model, that markedly edematous ("translucent") white matter regions (> 10% increases in water contents) containing high levels of clot-derived plasma proteins rapidly develop adjacent to hematomas. The goal of the present study was to determine the concentrations of high-energy phosphate, carbohydrate substrate, and lactate in these and other perihematomal white and gray matter regions during the early hours following experimental ICH. METHODS: The authors infused autologous blood (1.7 ml) into frontal lobe white matter in a physiologically controlled model in pigs (weighing approximately 7 kg each) and froze their brains in situ at 1, 3, 5, or 8 hours postinfusion. Adenosine triphosphate (ATP), phosphocreatine (PCr), glycogen, glucose, lactate, and water contents were then measured in white and gray matter located ipsi- and contralateral to the hematomas, and metabolite concentrations in edematous brain regions were corrected for dilution. In markedly edematous white matter, glycogen and glucose concentrations increased two- to fivefold compared with control during 8 hours postinfusion. Similarly, PCr levels increased several-fold by 5 hours, whereas, except for a moderate decrease at 1 hour, ATP remained unchanged. Lactate was markedly increased (approximately 20 micromol/g) at all times. In gyral gray matter overlying the hematoma, water contents and glycogen levels were significantly increased at 5 and 8 hours, whereas lactate levels were increased two- to fourfold at all times. CONCLUSIONS: These results, which demonstrate normal to increased high-energy phosphate and carbohydrate substrate concentrations in edematous perihematomal regions during the early hours following ICH, are qualitatively similar to findings in other brain injury models in which a reduction in metabolic rate develops. Because an energy deficit is not present, lactate accumulation in edematous white matter is not caused by stimulated anaerobic glycolysis. Instead, because glutamate concentrations in the blood entering the brain's extracellular space during ICH are several-fold higher than normal levels, the authors speculate, on the basis of work reported by Pellerin and Magistretti, that glutamate uptake by astrocytes leads to enhanced aerobic glycolysis and lactate is generated at a rate that exceeds utilization.

Lobar intracerebral hemorrhage model in pigs: rapid edema development in perihematomal white matter.

BACKGROUND AND PURPOSE: The mechanisms underlying brain injury from intracerebral hemorrhage (ICH) are complex and poorly understood. To comprehensively examine pathophysiological and pathochemical alterations after ICH and to examine the effects of hematoma removal on these processes, we developed a physiologically controlled, reproducible, large-animal model of ICH in pigs (weight, 6 to 8 kg). METHODS: We produced lobar hematomas by pressure- controlled infusions of 1.7 mL of autologous blood into the right frontal hemispheric white matter over 15 minutes. We froze brains in situ at 1, 3, 5, and 8 hours after hematoma induction and cut coronal sections of hematoma assessment, morphological brain examination, and immunohistochemical and water content determinations. RESULTS: At 1 hour after blood infusion, "translucent" white matter areas were present directly adjacent to the hematoma. These markedly edematous regions had a greater than 10% increase in water content (>85%) compared with the contralateral white matter (73%), and this increased water content persisted through 8 hours. In addition, these areas were strongly immunoreactive for serum proteins. Intravascular Evans blue dye failed to penetrate into the brain tissue at all time points, demonstrating that this serum protein accumulation and edema development were not due to increased blood-brain barrier permeability. CONCLUSIONS: Experimental lobar ICH in pigs models a prominent pathological feature of human ICH, ie, early perihematomal edema. Our findings suggest that serum proteins, originating from the hematoma, accumulate in adjacent white matter and result in rapid and prolonged edema after ICH. This interstitial edema likely corresponds to the low densities on CT scans and the hyperintensities on T2-weighted MR images that surround intracerebral hematomas acutely after human ICH.

Use of the Morris water maze and acoustic startle chamber to evaluate neurologic injury after asphyxial arrest in rats.

The study was performed to assess the utility of the Morris water maze (MWM) and acoustic startle reflex (ASR) for evaluating neurologic outcome in a rat model of asphyxial cardiac arrest. Rats were anesthetized, intubated, and chemically paralyzed. Control animals were decannulated and, after awakening, were extubated and returned to their housing. Experimental animals were asphyxiated by disconnecting the ventilator. Approximately 3.5 min after the disconnection, there was no measurable pulse. After 7 min of asphyxia, they were then resuscitated with resumed ventilation, chest compressions, epinephrine, and sodium bicarbonate. All animals were assigned to either MWM or ASR testing. The MWM is a 6-ft diameter tank filled with opaque water. In a fixed location of the tank, a 4-inch diameter escape platform is submerged just below the surface. MWM animals were tested on post-injury d 16-21 by recording the path and time taken to escape from three randomly assigned locations per d. ASR animals had s.c. leads placed over the right triceps and tibialis anterior muscles. The latency and rectified amplitude of the ASR was measured by recording the electromyographic impulse generated when the animal was startled by an acoustic stimulus. Animals were tested on post-injury d 6 and 7. After the last test session for each group, the animals' brains were removed for histopathologic examination. Asphyxiated MWM animals took longer to find the platform, and their paths were less direct than control animals (analysis of variance p < 0.05). The ASR of asphyxiated ASR animals had greater amplitude and shorter latency compared with controls (analysis of variance p < 0.05). Histologic examination revealed no abnormalities in control animals, but 80% of asphyxiated brains showed hippocampal neuronal injury and/or reactive gliosis in the CA1 segment. Abnormalities were more commonly detected in animals killed 7 d post-injury (ASR protocol) compared with animals killed 21 d post-injury (MWM protocol). We conclude that the MWM and ASR are useful for detecting neuronal injury in asphyxiated rats.