Regional cerebral blood flow after cortical impact injury complicated by a secondary insult in rats.

BACKGROUND AND PURPOSE: Traumatic injury makes the brain susceptible to secondary insults. An uncomplicated mild lateral cortical impact injury (3 m/s, 2.5-mm deformation) that causes little or no permanent sequelae results in a large contusion at the impact site when the traumatic injury is complicated by a secondary insult, such as 40 minutes of bilateral carotid occlusion. METHODS: To determine whether the increased sensitivity to secondary insults in this model is caused by a vascular mechanism, cerebral blood flow (CBF) was measured with (14)C-isopropyliodoamphetamine quantitative autoradiography, and brain tissue PO(2) (PbtO(2)) was measured at the impact site and in the contralateral parietal cortex. RESULTS: In animals that underwent bilateral carotid occlusion 1 hour after the impact injury, CBF and PbtO(2) were lower at the impact site than they were in animals that had either the impact injury or the carotid occlusion alone. In the immediate area of the impact, CBF was 14+/-6 mL. 100 g(-1). min(-1) in the animals with the impact injury followed by carotid occlusion compared with 53+/-24 mL. 100 g(-1). min(-1) in the animals with the impact injury alone and 74+/-14 mL. 100 g(-1). min(-1) in the animals with the carotid occlusion alone (P<0.001). At the time of this very low CBF value in the animals with the carotid occlusion after the impact injury, PbtO(2) at the impact site averaged 1.3+/-1.6 mm Hg and was <3 mm Hg in 5 of the 6 animals. In contrast, PbtO(2) in the animals with the impact injury alone averaged 9.3+/-2.9 mm Hg, and none of the animals had a PbtO(2) of <3 mm Hg (P=0.008). CONCLUSIONS: The CBF and PbtO(2) findings in this model suggest that the reduced CBF after traumatic injury predisposes the brain to secondary insults and results in ischemia when confronted with a reduction in cerebral perfusion pressure.

Cerebrovascular reactivity to CO(2) and hypotension after mild cortical impact injury.

Cerebrovascular reactivity to CO(2) or hypotension was studied in vivo and in vitro [pressurized arteries ( approximately 82 micrometer) and arterioles ( approximately 30 micrometer)] at 1 h after mild controlled cortical impact (CCI) injury in rats. The cortical perfusion response [assessed using laser-Doppler flowmetry (LDF)] to altered CO(2) was diminished (up to 81%) after mild CCI injury. The responses to CO(2) alterations in arteries and arterioles isolated from the injured cortex were similar to responses in vessels isolated from sham-injured animals. After mild CCI injury, the autoregulatory response to hypotension (measured using LDF) was maintained or even enhanced, depending on the method used to measure the response. Vessels isolated from the injury site showed a response to changes in pressure similar to that in vessels isolated from sham-injured rats. We conclude that mild CCI injury produces complicated alterations in cerebrovascular control. Whereas the autoregulatory response to hypotension was maintained or even enhanced, the in vivo vascular response to CO(2) was severely compromised. The altered response to CO(2) was not caused by an intrinsic vascular perturbation but rather an altered milieu after mild CCI injury.

Regional changes in cerebral extracellular glucose and lactate concentrations following severe cortical impact injury and secondary ischemia in rats.

Traumatic brain injury (TBI) causes the brain to be more susceptible to secondary insults, and the occurrence of a secondary insult after trauma increases the damage that develops in the brain. To study the synergistic effect of trauma and ischemia on brain energy metabolites, regional changes in the extracellular concentrations of glucose and lactate following a severe cortical impact injury were measured employing a microdialysis technique. Three microdialysis probes were placed in center of the impact site, in an area adjacent to the impact site, and in the contralateral parietal cortex, and perfused with artificial cerebrospinal fluid (CSF) at 2 microl/min. Rats were assigned to one of the following experimental groups (n = 7 per group): (1) combined impact injury and secondary insult, (2) impact injury with sham secondary insult, (3) sham impact with secondary insult, or (4) sham impact and sham secondary insult. The impact injury was produced with a pneumatic impactor (5 m/sec, 3-mm deformation). One hour following the impact injury, a secondary insult was produced by bilateral carotid occlusion for 1 h. The impact injury resulted in a three- to fivefold global increase in dialysate lactate concentrations, with a corresponding fall in dialysate glucose concentration by 50% compared to no change in lactate or glucose concentrations in sham-injured animals (p < .0001 for both lactate and glucose). The secondary insult resulted in a second increase in dialysate lactate and decrease in dialysate glucose concentration that was significantly greater in the animals that had suffered the impact injury than in the sham-injured animals. Ischemia and traumatic injury have synergistic effects on lactate accumulation and on glucose depletion in the brain that probably reflects persisting ischemia, but may also indicate mitochondrial abnormalities and inhibition of oxidative metabolism.

S-adenosylmethionine decarboxylase activity is decreased in the rat cortex after traumatic brain injury.

S-Adenosyl-L-methionine decarboxylase (SAMdc) and L-ornithine decarboxylase (ODC) are major enzymes regulating polyamine synthesis. Following ischemia, putrescine content increases as a result of posttraumatic activation of ODC and inhibition of SAMdc. These alterations are thought to mediate edema and cell death. The purpose of this study was to quantify SAMdc activity and edema in the brain following controlled cortical impact injury. Anesthetized adult male rats underwent a right parietal craniectomy and were subjected to cortical impact injury. Tissues were obtained from three bilateral regions: parietal cortex, motor area (CPm); parietal cortex, somatosensory area (CPs); and the pyriform cortex (CPF). SAMdc activity was determined in the postmitochondrial fraction from homogenates of fresh, unfrozen tissues by measuring the decarboxylation of S-adenosyl-L-[carboxyl-14C]methionine. Basal SAMdc activity was determined in unoperated rats, and regional differences were noted: Activity was lower in the CPF than in the CPm and CPs. SAMdc activity decreased to the greatest extent in the ipsilateral CPm (impact site) from 1 to 72 h following traumatic brain injury. Significant edema was found in the ipsilateral CPm 1, 8, 16, 24, and 48 h after injury. Decreased SAMdc activity impairs the conversion of putrescine to polyamines and may contribute to delayed pathological changes in the brain after traumatic injury.