Propofol Pretreatment Fails to Provide Neuroprotection Following a Surgically Induced Brain Injury Rat Model.

Neurosurgical procedures are associated with unintentional damage to the brain during surgery, known as surgically induced brain injuries (SBI), which have been implicated in orchestrating structural and neurobehavioral deterioration. Propofol, an established hypnotic anesthetic agent, has been shown to ameliorate neuronal injury when given after injury in a number of experimental brain studies. We tested the hypothesis that propofol pretreatment confers neuroprotection against SBI and will reduce cerebral edema formation and neurobehavioral deficits in our rat population. Sprague-Dawley rats were treated with low- and high-dose propofol 30 min before SBI. At 24 h post injury, brain water content and neurobehavioral assessment was conducted based on previously established models. In vehicle-treated rats, SBI resulted in significant cerebral edema and higher neurological deficit scores compared with sham-operated rats. Low- or high-dose propofol therapy neither reduced cerebral edema nor improved neurologic function. The results suggest that propofol pretreatment fails to provide neuroprotection in SBI rats. However, it is possible that a SBI model with less magnitude of injury or that propofol re-dosing, given the short-acting pharmacokinetic property of propofol, may be needed to provide definitive conclusions.

Effects of hemodilution after traumatic brain injury in juvenile rats.

BACKGROUND: Normovolemic hemodilution (HD) in adult animal studies has shown exacerbation of traumatic brain injury (TBI) lesion volumes. Similar studies in juvenile rats have not been reported and outcomes are likely to be different. This study investigated the effects of normovolemic hemodilution (21% hematocrit) in a juvenile TBI (jTBI) model. METHODS: Twenty 17-day-old rats underwent moderate cortical contusion impact injury (CCI) and were divided into four groups: CCI/hemodilution (HD) (group HD), CCI/no HD (group C), Sham/HD (group SHD), and Sham/no HD (group S). Regional laser Doppler flowmetry (LDF), edema formation (MRI-T2WI), water mobility assessed using diffusion weighted imaging (MRI-DWI), open field activity tests, and histological analyses were evaluated for lesion characteristics. RESULTS: Hemodilution significantly increased blood flow in the HD compared to the C group after TBI. T2WI revealed a significantly increased extravascular blood volume in HD at 1, 7, and 14 days post-CCI. Edematous tissue and total contusional lesion volume were higher in HD-treated animals at 1 and 14 days. DWI revealed that HD, SHD, and C groups had elevated water mobility compared to S groups in the ipsilateral cortex and striatum. Histology showed a larger cortical lesion in the C than HD group. Open field activity was increased in HD, C, and SHD groups compared to the S group. CONCLUSIONS: Hemodilution results in significant brain hyperemia with increased edema formation, extravascular blood volume, and water mobility after jTBI. Hemodilution results in less cortical damage but did not alter behavior. Hemodilution is likely not to be clinically beneficial following jTBI.

3% hypertonic saline following subarachnoid hemorrhage in rats.

BACKGROUND: Hypertonic saline (HTS) has been proposed as a treatment after aneurysmal subarachnoid hemorrhage (SAH) to minimize ischemic brain injury due to its osmotic and rheologic properties. Although the benefits of 7.2% HTS use in brain injury have been studied, there is a paucity of data on the use of 3%HTS. METHODS: We investigated whether 3%HTS can reduce brain water content and improve neurologic function after SAH in the rodent model compared to 0.9% saline solution (NS). Neurologic testing was conducted at 24 hours post-SAH prior to sacrificing animals for brain water content evaluation. FINDINGS: There was significant potentiation of brain water content in the right hemisphere between 3%HTS and NS groups. The modified Garcia score was not significantly different between the two groups; however, the vibrissae-stimulated forelimb placement test showed significantly lower scores in the HTS group. 3%HTS does not decrease brain edema or improve neurologic deficits as compared to NS. In fact, our study showed 3%HTS potentiated brain edema and worsened neurologic deficits in the rat SAH model. CONCLUSIONS: Given the potential adverse effects of HTS therapies, including hyperchloremic acidosis, and the lack of benefit found in our study, more investigation is required to evaluate the clinical use of 3%HTS in the setting of SAH.

p53 may play an orchestrating role in apoptotic cell death after experimental subarachnoid hemorrhage.

OBJECTIVE: Secondary brain injury after subarachnoid hemorrhage (SAH) is poorly understood. As a result, there are few treatment options. Consequently, SAH is associated with a high rate of morbidity and mortality. In an effort to combat these problems, the role of apoptosis was examined in the whole brain after SAH. In particular, the role of p53 and the three major apoptotic cascades were studied, the caspase-dependent and caspase-independent cascades and the mitochondrial pathway. METHODS: In this study, 195 Sprague-Dawley rats were divided into three groups, including sham, nontreatment, and treatment (Pifithrin-alpha; BIOMOL, Inc., Plymouth Meeting, PA) groups. The monofilament puncture model was used to induce SAH and the animals were subsequently sacrificed at 24 and 72 hours. Western blot analysis, histology, physiological parameters, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling, and immunohistological techniques were used to demonstrate the role of p53 and the apoptotic cascades in the rat brain after SAH. In addition, outcome was determined based on mortality rates and neurological outcome scores. RESULTS: We found that p53 and associated apoptotic proteins were up-regulated after SAH and that downstream mediators of apoptosis were negatively influenced by the inhibition of p53 by Pifithrin-alpha. Furthermore, we found that apoptotic inhibition resulted in less cell death and an overall favorable outcome in the treated animals. CONCLUSION: These results suggest that apoptosis may be an important cause of cell death in the brain after SAH and that p53 may play an orchestrating role regarding apoptosis in SAH.