Temporal Changes in Intracranial Pressure
Temporal Changes in Intracranial Pressure
Object. The authors describe an experimental model of closed head injury in rodents that was modified from one developed by Marmarou and colleagues. This modification allows dual control of the dynamic process of impact compared with impulse loading that occurs at the moment of primary brain injury. The principal element in this weight-drop model is an adjustable table that supports the rat at the moment of impact from weights positioned at different heights (accelerations). The aim was to obtain reproducible pathological intracranial pressure (ICPs) while maximally reducing the incidence of mortality and skull fractures.
Methods. Intracranial pressure was investigated in different experimental settings, including two different rat strains and various impact-acceleration conditions and posttrauma survival times. Identical impact-acceleration injuries produced a considerably higher mortality rate in Wistar rats than in Sprague-Dawley rats (50% and 0%, respectively). Gradually increasing severity of impact-acceleration conditions resulted in findings of a significant correlation between the degree of traumatic challenge and increased ICP at 4 hours (p , 0.001, R = 0.73). When the impact-acceleration ratio was changed to result in a more severe head injury, the ICP at 4, 24, and 72 hours was significantly elevated in comparison with that seen in sham-injured rats (4 hours: 19.7 ± 2.8 mm Hg, p = 0.004; 24 hours: 21.8 ± 1.1 mm Hg, p = 0.002; 72 hours: 11.9 ± 2.5 mm Hg, p = 0.009). Comparison of the rise in ICP between moderate and severe impactacceleration injury at 4 and 24 hours revealed a significantly higher value after severe injury (4 hours: p = 0.008; 24 hours: p = 0.004). Continuous recordings showed that ICP mounted very rapidly to peak values, which declined gradually toward a pathological level dependent on the severity of the primary insult. Histological examination after severe trauma revealed evidence of irreversible neuronal necrosis, diffuse axonal injury, petechial bleeding, glial swelling, and perivascular edema.
Conclusions. This modified closed head injury model mimics several clinical features of traumatic injury and produces reliable, predictable, and reproducible ICP elevations with concomitant morphological alterations.
Traumatic brain injury (TBI) initiates a broad range of complex mechanical and pathophysiological destructive cascades and hence is associated with high mortality and morbidity rates. In blunt head trauma, primary brain injury results in focal or diffuse damage. Secondary events inflicted on an already ravaged brain may be even more detrimental to its function than the initial insults. Despite progressive improvements in the management of severe head trauma throughout the years, neurotrauma remains a serious public health problem. In the United States each year more than 2,000,000 individuals present at hospitals with a head injury. Of these, approximately 75,000 die, 2000 live in a vegetative state, 500 develop epileptic seizures, and another 125,000 endure lifelong debilitating loss of function. A study conducted by the Traumatic Coma Data Bank study group revealed that approximately 55% of patients who were comatose on admission suffered from diffuse brain injury. Although considerable and profound research efforts as well as clinical investigations have been conducted, the standard guidelines concerning the treatment of severe head injury have not changed substantially compared with measures recommended a decade ago.
Several groups of investigators have developed animal models of TBI in an attempt to reproduce various aspects of the pathophysiological responses, neurological syndromes, and histopathological findings observed in human head injury. Two reciprocal hypotheses are implicit in brain injury modeling: 1) that TBI in humans can be duplicated in nonhumans; and 2) that TBI in nonhuman models replicates human injury. Among the plethora of experimental models, the most commonly used are closed head injury and percussion models. The latter preferentially produce a focal brain contusion. Artifacts resulting from the experimental methodology (for example, blood pressure surge and craniotomy) not only complicate the findings, but they also show biomechanical differences with most common clinical trauma cases. Therefore, a closed head injury impact-acceleration model was chosen and modified to allow adjustment of the dynamic impact-acceleration process, including variations in impact loading (contusion) and impulse loading (concussion). We reasoned that limitation of the extraneous influences inherent to the experimental methodology, as well as the conceptual approximation, should make the model more reliable and reproducible and hence might improve its clinical relevance. In analogy with the clinical situation, the severity of brain damage was estimated by using intracranial pressure (ICP) measurements performed at different time intervals after various impact-acceleration traumas. Furthermore, an absolute prerequisite in this model besides a rise in ICP is the presence of morphological alterations comparable to those encountered in clinical neuropathology. Finally, the model aimed to reduce the mortality rate and skull fractures as much as possible. Preliminary results of this study were published in the proceedings of the 10th Brain Edema Congress.
Object. The authors describe an experimental model of closed head injury in rodents that was modified from one developed by Marmarou and colleagues. This modification allows dual control of the dynamic process of impact compared with impulse loading that occurs at the moment of primary brain injury. The principal element in this weight-drop model is an adjustable table that supports the rat at the moment of impact from weights positioned at different heights (accelerations). The aim was to obtain reproducible pathological intracranial pressure (ICPs) while maximally reducing the incidence of mortality and skull fractures.
Methods. Intracranial pressure was investigated in different experimental settings, including two different rat strains and various impact-acceleration conditions and posttrauma survival times. Identical impact-acceleration injuries produced a considerably higher mortality rate in Wistar rats than in Sprague-Dawley rats (50% and 0%, respectively). Gradually increasing severity of impact-acceleration conditions resulted in findings of a significant correlation between the degree of traumatic challenge and increased ICP at 4 hours (p , 0.001, R = 0.73). When the impact-acceleration ratio was changed to result in a more severe head injury, the ICP at 4, 24, and 72 hours was significantly elevated in comparison with that seen in sham-injured rats (4 hours: 19.7 ± 2.8 mm Hg, p = 0.004; 24 hours: 21.8 ± 1.1 mm Hg, p = 0.002; 72 hours: 11.9 ± 2.5 mm Hg, p = 0.009). Comparison of the rise in ICP between moderate and severe impactacceleration injury at 4 and 24 hours revealed a significantly higher value after severe injury (4 hours: p = 0.008; 24 hours: p = 0.004). Continuous recordings showed that ICP mounted very rapidly to peak values, which declined gradually toward a pathological level dependent on the severity of the primary insult. Histological examination after severe trauma revealed evidence of irreversible neuronal necrosis, diffuse axonal injury, petechial bleeding, glial swelling, and perivascular edema.
Conclusions. This modified closed head injury model mimics several clinical features of traumatic injury and produces reliable, predictable, and reproducible ICP elevations with concomitant morphological alterations.
Traumatic brain injury (TBI) initiates a broad range of complex mechanical and pathophysiological destructive cascades and hence is associated with high mortality and morbidity rates. In blunt head trauma, primary brain injury results in focal or diffuse damage. Secondary events inflicted on an already ravaged brain may be even more detrimental to its function than the initial insults. Despite progressive improvements in the management of severe head trauma throughout the years, neurotrauma remains a serious public health problem. In the United States each year more than 2,000,000 individuals present at hospitals with a head injury. Of these, approximately 75,000 die, 2000 live in a vegetative state, 500 develop epileptic seizures, and another 125,000 endure lifelong debilitating loss of function. A study conducted by the Traumatic Coma Data Bank study group revealed that approximately 55% of patients who were comatose on admission suffered from diffuse brain injury. Although considerable and profound research efforts as well as clinical investigations have been conducted, the standard guidelines concerning the treatment of severe head injury have not changed substantially compared with measures recommended a decade ago.
Several groups of investigators have developed animal models of TBI in an attempt to reproduce various aspects of the pathophysiological responses, neurological syndromes, and histopathological findings observed in human head injury. Two reciprocal hypotheses are implicit in brain injury modeling: 1) that TBI in humans can be duplicated in nonhumans; and 2) that TBI in nonhuman models replicates human injury. Among the plethora of experimental models, the most commonly used are closed head injury and percussion models. The latter preferentially produce a focal brain contusion. Artifacts resulting from the experimental methodology (for example, blood pressure surge and craniotomy) not only complicate the findings, but they also show biomechanical differences with most common clinical trauma cases. Therefore, a closed head injury impact-acceleration model was chosen and modified to allow adjustment of the dynamic impact-acceleration process, including variations in impact loading (contusion) and impulse loading (concussion). We reasoned that limitation of the extraneous influences inherent to the experimental methodology, as well as the conceptual approximation, should make the model more reliable and reproducible and hence might improve its clinical relevance. In analogy with the clinical situation, the severity of brain damage was estimated by using intracranial pressure (ICP) measurements performed at different time intervals after various impact-acceleration traumas. Furthermore, an absolute prerequisite in this model besides a rise in ICP is the presence of morphological alterations comparable to those encountered in clinical neuropathology. Finally, the model aimed to reduce the mortality rate and skull fractures as much as possible. Preliminary results of this study were published in the proceedings of the 10th Brain Edema Congress.
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