Intracerebral adult stem cells transplantation increases brain-derived neurotrophic factor levels and protects against phencyclidine-induced social deficit in mice.

Stem cell-based regenerative therapy is considered a promising cellular therapeutic approach for the patients with incurable brain diseases. Mesenchymal stem cells (MSCs) represent an attractive cell source for regenerative medicine strategies for the treatment of the diseased brain. Previous studies have shown that these cells improve behavioral deficits in animal models of neurological disorders such as Parkinson's and Huntington's diseases. In the current study, we examined the capability of intracerebral human MSCs transplantation (medial pre-frontal cortex) to prevent the social impairment displayed by mice after withdrawal from daily phencyclidine (PCP) administration (10 mg kg(-1) daily for 14 days). Our results show that MSCs transplantation significantly prevented the PCP-induced social deficit, as assessed by the social preference test. In contrast, the PCP-induced social impairment was not modified by daily clozapine treatment. Tissue analysis revealed that the human MSCs survived in the mouse brain throughout the course of the experiment (23 days). Significantly increased cortical brain-derived neurotrophic factor levels were observed in the MSCs-treated group as compared with sham-operated controls. Furthermore, western blot analysis revealed that the ratio of phosphorylated Akt to Akt was significantly elevated in the MSCs-treated mice compared with the sham controls. Our results demonstrate that intracerebral transplantation of MSCs is beneficial in attenuating the social deficits induced by sub-chronic PCP administration. We suggest a novel therapeutic approach for the treatment of schizophrenia-like negative symptoms in animal models of the disorder.

Influence of pharmaceutical gel vehicles containing oleic acid/sodium oleate combinations on hairless mouse skin, a histological evaluation.

Aqueous gel preparations containing oleic acid/sodium oleate combinations were applied three times daily to hairless mice (CD1 strain). Six groups of animals (n = 9 or n = 10) were treated topically with six experimental vehicles containing 2, 3 and 4.5% oleic acid (OA) at two different pH values, 7.3 and 7.7. Sodium lauryl sulfate (5%) in a similar gel preparation was used as the positive control (n = 5), while untreated animals were used as the negative control (n = 6). After three treatment days, the skin samples were collected and processed for histological evaluation. It was seen that the severity and frequency of histological changes in the skin treated with OA-containing vehicles were directly correlated with increased pH/ionization (i.e. decreased OA/sodium oleate ratio) and with overall OA concentration.