Article
Closed traumatic brain injury in sheep: Correlation of multiparametric neuromonitoring and histopathological findings
Das geschlossene Schädel-Hirn-Trauma beim Schaf: Korrelation multiparametrischer Neuromonitoring-Daten und histopathologischer Ergebnisse
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Published: | April 11, 2007 |
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Objective: Traumatic brain injury (TBI) initiates a complex cascade of cellular and molecular changes resulting in structural and neuronal brain damage. However, the exact interrelation of cellular changes and neuronal injuries during TBI needs to be elucidated. Various experimental models imitate only parts of the mechanisms of human TBI. Sharing similar trauma mechanics and pathophysiological mechanisms, the modified ovine closed TBI model allows us to simulate different degrees of human head injury.
Methods: Due to the large gyrencephalic brain and flexible cervical spine, sheep are ideal for neurotraumatological research. The basic of our modified impact acceleration model was the captive bolt model designed by Lewis et al (1996). To avoid skull fractures during the experiments, an anatomically shaped rubber bolt with an integrated oscillation absorber was developed. A frame construction for constant trauma parameters guarantees a highly reproducible trauma. Eight sheep (sham n=3) were anesthetized and ventilated. Head injury was induced with a modified non-penetrating captive stunner to the temporal region of the unrestrained head. A charge of 7.2 kN was used for the mild TBI group (n=3) and one of 10.5 kN for the severe TBI group (n=2). After trauma, cerebral tissue oxygen, carbon dioxide partial pressure, pH, temperature and intracranial pressure (ICP) were measured. In addition, intracerebral microdialysis (glutamate, aspartate, GABA, taurine, glycine) was conducted. The brain was histologically and immunohistochemically examined for apoptotic processes and axonal injuries fifteen hours after the impact.
Results: The severely traumatized animals showed a higher ICP (18,1+7,2 mmHg) in comparison to the sham group (9,9+2,6 mmHg) and to the mild TBI group (10,8+2,5 mmHg). Cerebral microdialysis of sheep with mild TBI showed an increase in glycine (236+133 µmol/l) and taurine (181+98 µmol/l) concentrations in comparison to the sham group (glycine: 26+13 µmol/l; taurine: 5+3 µmol/l). The neuropathological examination of the severely head injured group revealed generalized edema, traumatic subarachnoidal haemorrhage and intracranial contusions. Immunohistochemistry demonstrated apoptotic processes and diffuse axonal injury.
Conclusions: The modified ovine closed TBI model enables us to investigate traumatic brain injuries of different severity. According to the pathological findings, increase in intracereberal concentrations of glycine and taurine without increase of glutamate indicates mild traumatic brain injury.