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Bone marrow-derived mesenchymal stem cells (BM-MSC) are considered as a potential therapeutic tool in neurodegenerative diseases, due to their ability to migrate to degenerated tissues and the production of growth factors. Congenital hydrocephalus is a disorder characterized by a degeneration of the periventricular cerebral parenchyma and the white matter. In the present study, using an animal model of congenital hydrocephalus, the hyh mouse, it has been studied the capacity of the BM-MSC to reach the degenerated regions exhibiting glial reactions and their probable neuroprotector effects. The BM-MSC were isolated from two sources: a) transgenic mice expressing the monomeric red fluorescent protein (mRFP1); b) wild type mice. In the second case, the BM-MSC were labelled in vitro using bromodeoxyuridine, a fluorescent cell tracker and the lipophilic DiR. Before application, the cells were analysed using flow cytometry and immunofluorescence. The BM-MSC were injected into the retro-orbital sinus or into the lateral ventricle of hyh mice. After 24/96 hours of administration, they were detected under light, confocal and electron microscopes. The injected BM-MSC reached the degenerated periventricular regions and the disrupted neurogenic niches. They were detected in the periventricular parenchyma, around periventricular blood vessels and in the ventral meninges. Most of the applied BM-MSC expressed the glial cell-derived neurotrophic factor (GDNF), in the same way as the periventricular reactive astrocytes, suggesting a possible neuroprotector effect. Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tech. Instituto de Salud Carlos III, PI12/0631 con cofinanciación FEDER.

Congenital hydrocephalus is a disorder presenting a degeneration of the periventricular cerebral parenchyma and the white matter, which causes significant mortality and life-long neurological complications. There are currently no effective therapies for congenital hydrocephalus. Bone marrow-derived mesenchymal stem cells (BM-MSC) are considered as a potential therapeutic tool in neurodegenerative diseases, due to their ability to migrate to degenerated tissues and the production of growth factors. In the present study, using an animal model of congenital hydrocephalus, the hyh mouse, it has been studied the capacity of the BM-MSC to reach the degenerated regions exhibiting glial reactions and their probable neuroprotector effects. The BM-MSC were isolated from two different sources: a) transgenic mice expressing the monomeric red fluorescent protein (mRFP1); b) wild type mice. In the second case, the BM-MSC were labelled in vitro using bromodeoxyuridine, a fluorescent cell tracker and the lipophilic DiR. Before application, the cells were analysed using flow cytometry and immunofluorescence. The BM-MSC were injected into the retro-orbital sinus or into the lateral ventricle of hyh mice. After 24/96 hours of administration, the BM-MSC were detected under light, confocal and electron microscopes. The injected BM-MSC reached the degenerated periventricular regions and the disrupted neurogenic niches. They were detected in the periventricular parenchyma, around periventricular blood vessels and in the ventral meninges. Most of the applied BM-MSC expressed the glial cell-derived neurotrophic factor (GDNF), in the same way as the periventricular reactive astrocytes, suggesting a possible neuroprotector effect. FIS (Instituto de Salud Carlos III)-FEDER a AJJ. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Background: Changes in the profile of metabolites in brain and/or fluids can be useful to evaluate the severity and evolution of hydrocephalus, and consequently to help in treatment decisions. Magnetic Resonance Spectroscopy can be used in ex vivo samples for such purposes. This study was designed to evaluate the levels of metabolites in the hyh mouse brain with congenital hydrocephalus by High Resolution Magic Angle Spinning (HR-MAS) Magnetic Resonance Spectroscopy (MRS). Materials and Methods: Wild type and hydrocephalic hyh mice at 30 days of postnatal age were sacrificed (n = 10-15 mice/disease condition), and hippocampus and neocortex were quickly dissected out, frozen in dry ice, and stored at -80ºC, before analysis by HR-MAS. Results: Similar levels of choline (Cho) were detected in the hippocampus and neorcortex of hydrocephalic mice compared to control samples, however phosphocholine (PCh) and glycerophosphorylcholine (GPC) displayed lower levels. These molecules are implied in the Kennedy pathway of phosphatidylcholine metabolism. The antioxidant tripeptide glutathione (GSH) was detected in higher quantities in the hydrocephalic mice, probably revealing a response to an oxidative metabolism. Other metabolites displayed remarkably higher levels in samples from hydrocephalic mice, such as creatine (Cr), taurine (Tau) and glutamine (Gln). Conclusions: HR-MAS was found as a reliable technique to detect differential levels of metabolites in small tissue biopsies samples from mice models with hydrocephalus. This technique represents a valuable tool for monitoring the degree of severity and/or the evolution of the disease in such models. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Supported by the grants PI12/0631 to AJJ; SERAM to MIML