Neuroprotective Effects of Nasopharyngeal Perfluorochemical Cooling in a Rat Model of Subarachnoid Hemorrhage.

OBJECTIVE: Subarachnoid hemorrhage (SAH) frequently results in severe morbidity, even mortality. Hypothermia is known to have a neuroprotective effect in ischemic injuries. The aim of this study was to determine whether nasopharyngeal (NP) perfluorochemical (PFC) cooling could be used in a rat model of SAH model for neuroprotection. METHODS: SAH was induced in 16 male Sprague-Dawley rats by cisterna magna injection of 0.3 mL autologous blood. Vital signs, temperatures, cerebral blood flow (CBF), and brain histology were assessed. Brain cooling was performed on the treatment group using the NP-PFC method starting from 20 minutes after SAH. RESULTS: No SAH-related deaths were observed in either group. SAH caused an immediate decrease in mean arterial pressure (17.0% ± 4.90% below baseline values). SAH induction caused a significant and rapid decrease in CBF from baseline (approximately -65%, ranging from -32% to -85%) in both hemispheres. In the left hemisphere, cooling facilitated the return of CBF to baseline values within 20 minutes of treatment with further increase in CBF that stabilized by the 2 hours after injury time point. Quantitative immunohistochemistry showed that there were significantly more NeuN-positive cells in the cortex and significantly fewer IBA-1-positive microglia and glial fibrillary acidic protein-positive astrocytes cells in both cortex and hippocampus in the animals that received NP-PFC cooling compared with no treatment, reflecting preserved neuronal integrity and reduced inflammation. CONCLUSIONS: The data from this study indicate that local hypothermia by NP-PFC cooling supports return of CBF and neuronal integrity and suppresses the inflammatory response in SAH, suggestive of a promising neuroprotective approach in management of SAH.

The antioxidant, MnTE-2-PyP, prevents side-effects incurred by prostate cancer irradiation.

Prostate cancer is the most commonly diagnosed cancer, with an estimated 240,000 new cases reported annually in the United States. Due to early detection and advances in therapies, more than 90% of patients will survive 10 years post diagnosis and treatment. Radiation is a treatment option often used to treat localized disease; however, while radiation is very effective at killing tumor cells, normal tissues are damaged as well. Potential side-effects due to prostate cancer-related radiation therapy include bowel inflammation, erectile dysfunction, urethral stricture, rectal bleeding and incontinence. Currently, radiation therapy for prostate cancer does not include the administration of therapeutic agents to reduce these side effects and protect normal tissues from radiation-induced damage. In the current study, we show that the small molecular weight antioxidant, MnTE-2-PyP, protects normal tissues from radiation-induced damage in the lower abdomen in rats. Specifically, MnTE-2-PyP protected skin, prostate, and testes from radiation-induced damage. MnTE-2-PyP also protected from erectile dysfunction, a persistent problem regardless of the type of radiation techniques used because the penile neurovascular bundles lay in the peripheral zones of the prostate, where most prostate cancers reside. Based on previous studies showing that MnTE-2-PyP, in combination with radiation, further reduces subcutaneous tumor growth, we believe that MnTE-2-PyP represents an excellent radioprotectant in combination radiotherapy for cancer in general and specifically for prostate cancer.