Biomedical subjects

C S Robertson

Publications and source records attributed to C S Robertson.

At least 55 records · Page 3Linked to original sources

PubMed1998

Hyperglycemia increases neurological damage and behavioral deficits from post-traumatic secondary ischemic insults.

The effects of post-traumatic administration of glucose 2.0 g/kg was compared to saline infusion with and without control of brain temperature at 37 degrees C on behavioral and histological measures of brain injury after controlled cortical impact injury complicated by a secondary ischemic insult. The glucose infusion increased blood glucose concentration from 114 +/- 4 to 341 +/- 76 mg/dl prior to the secondary ischemic insult. The resulting outcome measures were significantly worse in the glucose infusion group than in either control group. Mortality rate was significantly increased by the glucose administration, from 0% to 55% (p < 0.001). The median contusion volume was increased from 7.9 to 64.2 by glucose administration (p < 0.001) and the neuronal loss in the CA1 and CA3 areas of the hippocampus were greater in the glucose infusion group. In the animals that survived for the 2 weeks of behavioral studies, the duration of beam balance was shorter; the percent of animals that could balance on the beam for at least 60 s was less, the percent of animals that could perform the beam-walking task was less, and the length of time required to find the platform in the Morris water maze task was longer in the glucose infusion group. These studies demonstrate that the infusion of glucose after the cortical impact injury significantly increases the damage caused by post-traumatic ischemic insults. The adverse effect on neurological outcome could not be explained by the temperature effects of glucose infusion.

Animals↗

PubMed1998

Comparison of brain tissue oxygen tension to microdialysis-based measures of cerebral ischemia in fatally head-injured humans.

This study investigated the relationship between brain tissue oxygen tension (PbtO2) and cerebral microdialysate concentrations of several compounds in five patients with refractory intracranial hypertension after severe head injury. The following substances were assayed: lactate and glucose; the excitatory amino acids glutamate and aspartate; and the cations potassium, calcium, and magnesium. Glucose concentrations did not correlate with PbtO2, but lactate increased as PbtO2 decreased. The lactate/glucose ratio exhibited a close relationship to PbtO2, increasing sharply only when oxygen tension reached zero. Although glucose and oxygen eventually reached very low levels and zero, respectively, in these fatally head-injured patients, the terminal decrease in PbtO2 slightly preceded that of glucose in four of the five patients. This time lag is the cause of the poor correlation between glucose and PbtO2. Glutamate and aspartate concentrations both demonstrated a close relationship to PbtO2, with sharp increases not occurring until PbtO2 was zero. Concentrations of these amino acids exhibited a similar pattern in response to decreasing glucose concentrations. Potassium concentrations began increasing at a PbtO2 of 35 mm Hg, which is not generally considered indicative of hypoxia. Sharper increases began occurring once PbtO2 dropped below 15 mm Hg, with a slight rise in the minimum potassium concentrations recorded at these low PbtO2 values. Calcium and magnesium concentrations did not vary in response to PbtO2. In summary, the most robust biochemical indicators of cerebral anoxia were elevations in the lactate/glucose ratio and in the concentrations of lactate and of the excitatory amino acids glutamate and aspartate. Furthermore, the fact that glucose concentrations continue to decrease for a short period after oxygen levels reach zero suggests that cells continue to utilize glucose anaerobically for such functions as maintenance of cellular integrity, with collapse of the cell membrane as evidenced by increases of extracellular glutamate and aspartate not occurring until both oxygen and glucose concentrations reach zero.

Adult↗

PubMed1998

Endothelial-mediated dilations following severe controlled cortical impact injury in the rat middle cerebral artery.

The mechanisms associated with dysfunction of the cerebral vasculature following head trauma have not yet been fully elucidated. In an attempt to shed more light on the matter, we investigated the endothelial-mediated dilations in the rat middle cerebral artery (MCA) following severe traumatic brain injury (TBI). Rats were subjected to severe controlled cortical impact injury (CCI; 5 m/s, 130 ms duration, 3 mm deformation) over the right parietal cortex. At 24 h postinjury, ipsilateral segments of MCA and corresponding contralateral segments were isolated, mounted in a vessel chamber, and pressurized. The responses to 2 methylthio-ATP (2MeSATP), a selective agonist for the P2Y1 purinoceptors, N(omega)-nitro-L-arginine (L-NAME), an NO synthase inhibitor, and S-nitroso-N-acetylpenicillamine (SNAP), an exogenous NO donor, were determined. 2MeSATP elicited concentration dependent dilations in all MCAs studied. Ipsilateral MCAs harvested following TBI or sham-TBI, showed similar maximum dilations to 2MeSATP [70 +/- 4% (n = 17) and 72 +/- 6% (n = 13), respectively]. However, TBI reduced the concentration of 2MeSATP necessary to elicit one-half of the maximum dilation (EC50) from 15 to 9 nM (p < 0.05). Inhibition of NO synthase with 10(-5) M L-NAME abolished the dilation to 2MeSATP in both TBI and sham-TBI MCAs. The constriction to L-NAME was significantly reduced in TBI MCAs compared to sham vessels. Dilations to SNAP, an NO donor, were not altered by TBI indicating that the mechanisms of dilation involving NO in the vascular smooth muscle were not affected. Unlike other pathological conditions which often diminish endothelial-mediated responses, severe TBI enhanced the sensitivity to 2MeSATP without altering the maximum response.

Adenosine Triphosphate↗

PubMed1998

Temporal effect of severe controlled cortical impact injury in the rat on the myogenic response of the middle cerebral artery.

The present study examined the effect of severe traumatic brain injury (TBI) on the myogenic response in the rat middle cerebral artery (MCA). Rats were subjected to severe controlled cortical impact (CCI; 5 m/sec, 130-msec duration, 3-mm deformation) injury over the right parietal cortex. At 2, 24, and 120 h postinjury, ipsilateral and contralateral segments of MCAs were isolated, mounted in a vessel chamber, and pressurized. After equilibration, the myogenic tone, the difference in vessel diameter in the presence and absence of calcium for a given pressure, and the myogenic response (the active contractile response elicited by a vessel to increasing pressure), were measured. At 24 h postsurgery, there was a significant interaction between myogenic tone and pressure in the ipsilateral and contralateral MCAs when TBI was compared to shams. However, this was not apparent, at the 2- and 120-h time points. At 2- and 24-h postsurgery, there was a significant interaction between myogenic response and pressure in the ipsilateral MCAs when TBI was compared to shams. While the response of the vascular smooth muscle was altered following injury, it was still functioning, suggesting that these vessels compensate, perhaps through alternate mechanisms or by relying on those remaining intact mechanisms.

Animals↗

PubMed1998

Brain temperature exceeds systemic temperature in head-injured patients.

OBJECTIVE: To identify the temperature differences in readings taken from the brain, jugular bulb, and core body in head-injured patients. DESIGN: Prospective, observational study. SETTING: Neurosurgical intensive care unit of a university-affiliated county hospital. PATIENTS: Thirty patients with severe head injuries had measurements of brain and core body temperatures. Fourteen patients also had measurements of jugular venous blood at the level of the jugular bulb. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Brain temperature was increased an average of 2.0 degrees F (1.1 degrees C) over the core body temperature. In individual patients, the average brain temperature increase over the core body temperature ranged from -0.5 degrees to 3.8 degrees F (-0.30 degrees to 2.1 degrees C). Jugular vein and core body temperatures were similar. The difference in the brain and body temperatures increased when cerebral perfusion pressure decreased to between 20 and 50 mm Hg. The difference in the brain and body temperatures decreased in those patients treated with barbiturate coma. CONCLUSIONS: Direct measurement of temperature in head-injured patients is a safe procedure. Temperatures in the brain are typically increased over the core body temperature and the jugular bulb temperatures. Jugular vein temperature measurement is not a good measurement of brain temperature since it reflects body, not brain temperature. These findings support the potential importance of monitoring brain temperature and the importance of controlling fever in severely head-injured patients since brain temperature may be higher than expected.

Adult↗

PubMed1998

Relationship of brain tissue PO2 to outcome after severe head injury.

OBJECTIVE: To determine thresholds of brain tissue PO2 (PbtO2) that are critical for survival after severe head injury. DESIGN: Prospective data collection. SETTING: Neurosurgical intensive care unit of Ben Taub General Hospital, a comprehensive academic neurosurgical facility and Level I trauma center. PATIENTS: Forty-three severely head-injured patients who were not obeying commands on presentation or whose condition deteriorated to this level shortly after admission. INTERVENTIONS: Intracerebral placement of Licox (n=39) or Paratrend (n=4) PO2 probes during craniotomy or in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: PbtO2 monitoring continued for an average of 84.6+/-41.8 hrs. The probes were calibrated before insertion according to the manufacturer's specifications. After removal, probes were tested in room air and in blood gas standard calibration solutions. PbtO2 data were analyzed by comparing the average time that PbtO2 was below the values of 20, 15, 10, 8, 6, 4, and 2 torr (2.7, 2.0, 1.3, 1.0, 0.8, 0.5, and 0.3 kPa, respectively) in patients who were living 3 mos after injury vs. those who died. A Tobit regression analysis using maximum likelihood methods was utilized. Both Licox and Paratrend probes functioned well in room air and in the Level I control. However, in the zero-oxygen solution, the Paratrend probes gave an average reading of 7.0+/-1.4 torr (0.9+/-0.2 kPa), compared with 0.3+/-0.3 torr (0.04+/-0.04 kPa) for the Licox probes. CONCLUSIONS: Analysis of the PbtO2 monitoring data suggested that the likelihood of death increased with increasing duration of time at or below a PbtO2 of 15 torr (2.0 kPa) or with the occurrence of any PbtO2 values of < or =6 torr (< or =0.8 kPa).

Adolescent↗

PubMed1997

Monitoring of cerebral hemodynamics with jugular bulb catheters.

Jugular venous oxygen saturation (SjvO2) monitoring is useful for detecting episodes of cerebral hypoxia/ischemia in patients with head injury, patients undergoing neurosurgical procedures, and patients undergoing cardiopulmonary bypass. The use of SjvO2 monitoring can direct the treatment of ischemic episodes and identify the optimal level of cerebral perfusion pressure and PCO2 for the individual patient.

Brain Ischemia↗

PubMed1997

Reduction in thermal hyperalgesia by intrathecal administration of glycine and related compounds.

We have previously shown in animal models that enhanced segmental glycine release is produced by neuroaugmentation techniques commonly used to control pain in humans. Our current hypothesis is that glycine administered intrathecally reduces the pain response evoked by the hotplate analgesia meter method. Neuropathic rats created by unilateral partial ligation of the sciatic nerve were treated with intrathecal infusion of glycine, strychnine, MK-801, or 5-7 DKA at 0.1 mumol for 2 hours at a rate of 10 microliters/min. Time required for limb withdrawal at 42 degrees C was significantly increased after glycine administration but not altered by strychnine, a specific glycine receptor antagonist. Administration of the NMDA receptor antagonist, MK-801, blocked the influence of glycine, with a less obvious antagonistic response from 5.7 DKA. Our results provide evidence that glycine and related compounds significantly modify thermal hyperalgesia, and may operate primarily through the NMDA receptor complex.

Analgesia, Epidural↗

PubMed1997

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.

Adenosylmethionine Decarboxylase↗

PubMed1997

Effects of anesthesia on polyamine metabolism and water content in the rat brain.

Because variances have been noted in brain putrescine levels of anesthetized rats (control, SHAM-operated), we investigated the effects of several anesthetics on polyamine metabolism and water content in the adult rat brain. Short duration (5 min) anesthesia was studied in three groups: ketamine:xylazine [KX; 40 and 8 mg/kg, respectively, intraperitoneal injection (IP)], urethane (UR; 1.5 g/kg, IP), and isoflurane (IF, initially 3.5% in 100% O2, followed by a maintenance dose of 2.5% IF in 100% O2). Effects of IF at longer duration (30 min) were also studied because this paradigm is often used in our laboratory. Control rats received no anesthesia (NA). Following decapitation, tissue samples were obtained from 3 bilateral brain regions: parietal cortex, motor area (CPm); parietal cortex, somatosensory area (CPs); and the pyriform cortex (CPF). The polyamines, spermidine and spermine, and their precursor, putrescine, were quantified by HPLC-fluorometric detection and brain water content was determined by wet-to-dry weight measures. KX decreased putrescine (54%) and spermidine (20%) in the CPs, increased spermine (24%) in the CPF, and increased water content in all brain regions. UR decreased putrescine (51%) and slightly increased water content (0.7%) in the CPF. Short duration IF decreased putrescine and spermidine in all brain regions; decreased spermine in the CPm, and increased water content in the CPF (0.8%). In contrast, longer duration IF increased putrescine (181%) and spermidine (23%) in the CPm, with no change in water content. Anesthetics produce region-specific changes in putrescine, polyamines, and water content in the rat brain which could contribute to the experimental variability.

Anesthesia, General↗

PubMed1997

Hyperglycemia increases brain injury caused by secondary ischemia after cortical impact injury in rats.

OBJECTIVE: To examine the effects of glucose infusion on the histologic brain damage caused by controlled cortical impact injury alone and by cortical impact injury complicated by secondary ischemia. DESIGN: Prospective, randomized study. SETTING: University laboratory. SUBJECTS: Male Long-Evans rats. INTERVENTIONS: Three experimental conditions were studied: a) 2.5-mm deformation impact (velocity 4 m/sec) injury followed by 40 mins of bilateral carotid occlusion; b) sham impact injury followed by 40 mins of bilateral carotid occlusion; and c) 2.5-mm deformation impact (velocity 4 m/sec) injury followed by sham carotid occlusion. For each experimental condition, animals were randomized to receive either glucose solution or saline solution before the induced injury and the sham impact injury. Contusion volume and neuron density in the CA1 and CA3 regions of the hippocampus were measured 2 wks after the injury. MEASUREMENTS AND MAIN RESULTS: Parenteral administration of 2.2 g/kg glucose solution increased the blood glucose concentration from 6.7 +/- 3.3 to 17.9 +/- 10.6 mmol/L before the impact injury, and to 12.3 +/- 5.6 mmol/L before carotid occlusion. Hyperglycemia had the greatest effect on the consequences of the impact injury complicated by secondary ischemia, increasing contusion volume from 1 to 30.6 mm3 in the animals that received saline or glucose solution, respectively (p = .005), and reducing the density of normal appearing neurons in the CA1 area of the hippocampus from 201 to 144 cells/mm2 in the animals that received saline solution and glucose solution, respectively (p = .038). The impact injury alone and bilateral carotid occlusion alone caused minimal neuronal loss in the hippocampus and minimal contusion or infarction at the impact site. Individually, these mild injuries were not adversely affected by infusion of glucose solution. CONCLUSION: Hyperglycemia increases brain damage when traumatic brain injury is complicated by secondary ischemia.

Animals↗

PubMed1997

Cerebral oxygenation during warming after cardiopulmonary bypass.

OBJECTIVES: To evaluate jugular venous oxygen saturation (SjVO2), measured with a fiberoptic oximetry catheter, and brain tissue oxygen saturation, measured by near-infrared spectroscopy (NIRSO2), as monitors of cerebral oxygenation during cardiopulmonary bypass surgery. DESIGN: Prospective, clinical study. SETTING: Operating room of a Veterans Administration Hospital. PATIENTS: Nineteen patients undergoing moderate hypothermic cardiopulmonary bypass surgery. INTERVENTIONS: SjvO2 and NIRSO2 were monitored in the patients during the surgical procedure. MEASUREMENTS AND MAIN RESULTS: Moderate hypothermic cardiopulmonary bypass surgery had two distinct cerebral hemodynamic phases. While the patients were hypothermic, SjvO2 averaged 80 +/- 7% and none of the patients had an increase in cerebral lactate production. During the rewarming period, however, reductions in SjvO2 to < 50% occurred in 16 (84%) patients and increased cerebral anaerobic metabolism developed in 11 (58%) patients. SjvO2 during rewarming was dependent on mean arterial pressure, with 60 mm Hg appearing to be a critical value. Two other factors appeared to also contribute to the jugular desaturation, a low hematocrit and a rapid warming time. The SjvO2 catheter had excellent performance during the surgery. The average difference between paired measurements of SjvO2 by the catheter and in blood samples was -0.4 +/- 4.25%, and the correlation between the two measurements was highly significant (r2 = .93; p < .001). The NIRSO2 trended with the SjvO2 in most patients (r2 = .63; p < .001). CONCLUSIONS: The study confirms other studies showing that jugular venous desaturation can occur during rewarming after cardiopulmonary bypass surgery. Presently, SjvO2 appears to be a better monitor of cerebral oxygenation than NIRSO2. However, NIRSO2 has promise as a noninvasive monitor of cerebral oxygenation if future developments allow more quantitative measurements of oxygen saturation.

Aged↗

PubMed1997

Positive end expiratory pressure reduces intracranial compliance in the rabbit.

Acute respiratory distress syndrome is commonly encountered in head-injured patients. Positive and expiratory pressure (PEEP) is useful in improving oxygenation. However, PEEP, by increasing intrathoracic pressure, decreases venous return, mean arterial pressure, and cardiac output and increases jugular vein pressure. There is conflicting evidence in the literature as to the potential effect of PEEP on intracranial pressure (ICP). The present study was undertaken to examine the effect of PEEP on ICP and intracranial compliance. Twelve male rabbits weighing 3.5-4.5 kg were used. The following parameters were monitored: arterial blood pressure, ICP (intraparenchymal Camino device), PaCO2, and PaO2. A space-occupying lesion was produced by inflation of a double lumen pediatric Swan-Ganz catheter placed over the right parietal dura. The amount of fluid required to reach the point of exponential increase of ICP was recorded at PEEP of 0 and 10 cm H2O. The mean volume needed to reach the deflection point of ICP was significantly lower when PEEP was 10 cm H2O compared to the value when PEEP was 0 cm H2O (685 +/- 48 vs. 883.3 +/- 46 microliters, respectively; p < 0.01). The results of the present study indicated that PEEP of 10 cm H2O decreases intracranial compensatory reserves for maintaining ICP at normal levels in the presence of an expanding intracranial mass.

Animals↗

PubMed1996

Lactic acid and amino acid fluctuations measured using microdialysis reflect physiological derangements in head injury.

We examined the extracellular neurochemical milieu in 34 head injured patients using microdialysis while simultaneously monitoring intracranial pressure, cerebral perfusion pressure, and jugular venous oxygen saturation. Derangements of anaerobic metabolism reflected by increased lactate and lactate/pyruvate ratios, and release of amino acids were seen at the same time as physiological deterioration in the majority of instances. Clinical microdialysis may provide insights into the neurochemistry of head injury, and such information may lead to new methods of monitoring and treating head injured patients.

Adult↗

PubMed1996

Evaluation of a regional oxygen saturation catheter for monitoring SjvO2 in head injured patients.

OBJECTIVES: Monitoring jugular venous oxygen saturation (SjvO2) has been useful for the early identification and treatment of cerebral ischemia in patients with severe head injury. However, the catheters that have been used for this purpose have not performed optimally. The purpose of this study was to evaluate the performance of a new regional oxygen saturation catheter for monitoring SjvO2. METHODS: Eighteen regional oxygen saturation catheters, 4-Fr in diameter (Baxter Healthcare Corporation, Edward Critical Care), were used in this study. Each catheter was inserted percutaneously into the dominant jugular vein and the catheter's tip position in the jugular bulb was verified by radiograph. The catheter was calibrated in vitro prior to insertion using the optic calibrator provided by the manufacturer. The catheter was recalibrated every 8 to 12 hours by comparing the oxygen saturation value from the catheter with that measured by a co-oximeter in a blood sample drawn through the catheter. RESULTS: In vitro calibration using the optic calibrator was not always successful. Five catheters could not be calibrated. The remaining 13 catheters could all be calibrated, but only 9 provided a value that was within 4% of the oxygen saturation derived from the blood sample. After the first in vivo calibration, the correlation between the catheter and the blood sample values was improved. A total of 196 comparisons were made. The median, 25th, and 75th quartile differences between the catheter and the blood sample measurement of SjvO2 were 0.00, -1.15, and 1.25%, respectively. Using longitudinal data regression, the overall slope of the regression between the catheter and blood values was 0.997 (p = 0.001). CONCLUSIONS: The new regional oxygen saturation catheter provided reliable measurement of SjvO2 83% of the time when the signal quality index was < or = 3, and may be useful for continuous monitoring of SjvO2.

Blood Gas Analysis↗

PubMed1996

Reduction in the mechanonociceptive response by intrathecal administration of glycine and related compounds.

We have previously reported that enhanced glycine release is produced by epidural spinal cord stimulation, a clinical method for treating neuropathic pain. Our current hypothesis is that glycine administered intrathecally reduces neuropathic pain as measured by the Randall-Selitto method. Neuropathic rats created by unilateral partial ligation of the sciatic nerve were treated with intrathecal infusion of glycine, strychnine, MK-801, or 5,7-DKA at 0.1 mumol, or artificial CSF for 2 hours at a rate of 10 microliters/min. Force required to produce the pain response was significantly increased after glycine administration and reduced using strychnine, a specific glycine receptor (Gly l) antagonist. Strychnine blocked the response to glycine when infused together. Administration of the non-specific NMDA receptor MK-801 antagonist and 5,7-DKA, a specific glycine-NMDA receptor (Gly 2) antagonist, however, failed to block the response to glycine. Our results provide evidence for the use of glycine and related compounds to treat neuropathic pain.

Animals↗

PubMed1996

The role of glycine in spinal shock.

Suppression of increased muscle tone by epidural spinal cord stimulation, an invasive method for treating spasticity, increases segmental concentrations of inhibitory amino acid neurotransmitters, particularly glycine. The role of glycine in spasticity and spinal shock was explored further in rabbits with ischemic spinal cord injuries that produced spastic paraparesis or flaccid paraplegia. H-reflexes were monitored following posterior tibial nerve stimulation and plantar surface recording. Spasticity was quantified by using H/M ratios. Spastic animals were intrathecally infused with 100 mmol/l solutions of glycine and related compounds. Glycine agonists suppressed tone whereas glycine antagonists increased tone. In addition, microdialysis sampling from the cord was done in injured, non-infused animals and aspartate, GABA, glutamate, glycine and taurine were measured. Flaccid animals had glycine levels two-three times higher than spastic or control animals. High concentrations of glycine within spinal cord segments is associated with spinal shock. Glycine and related compounds may be useful as treatment for excessive tone.

Amino Acids↗

PubMed1996

Secondary insults increase injury after controlled cortical impact in rats.

Secondary ischemic insults are common after severe head injury and contribute to poor neurological outcome. To study the increased vulnerability of the traumatized brain to secondary insults, bilateral carotid occlusion was produced after a controlled cortical impact injury in rats. The injury produced by either the impact injury or the bilateral carotid occlusion was mild to moderate when studied individually. The 1 and 3 m/sec impact injuries alone caused no detectable contusion at the impact side and minimal neuronal loss in the hippocampus. The 5 m/sec impact injury alone resulted in a small contusion with a median volume of 5.4 mm3. The 40-min period of bilateral carotid occlusion alone caused no cortical injury and no neuronal loss in the CA1 region of the hippocampus. When the 40 min of bilateral carotid occlusion was produced 1 h after the impact injury, there was an increase in the damage produced. The contusion volume was significantly larger after the 3 and 5 m/sec impact injuries and the hippocampal neuronal loss was significantly greater after the 1 and 3 m/sec impact injuries. When varying durations of bilateral carotid occlusion were produced 1 h after a 3 m/sec impact injury, contusion volume was significantly larger after bilateral carotid occlusion duration of 40 min, and CA1 neuronal loss was significantly greater after bilateral carotid occlusion durations of 30 and 40 min. When 40 min of bilateral carotid occlusion was produced at different time intervals after a 3 m/sec injury, the increased contusion volume was maximal when bilateral carotid occlusion occurred at 4 h after the impact injury, and the increased neuronal loss in the CA3 region of the hippocampus was maximal when bilateral carotid occlusion occurred at 1 h after the impact injury. By 24 h after the impact injury, 40 min of bilateral carotid occlusion had minimal consequences, similar to the effect in sham-injured animals. These results mimic the clinical situation where secondary insults of a severity that would not cause permanent neurological damage in a normal person are associated with a marked worsening of neurological outcome after head injury and where the injured brain is most susceptible to secondary insults in the first few hours after injury.

Animals↗