Neurorestoration Approach by Biomaterials in Ischemic Stroke.

Ischemic stroke (IS) is the leading cause of disability in the western world, assuming a high socio-economic cost. One of the most used strategies in the last decade has been biomaterials, which have been initially used with a structural support function. They have been perfected, different compounds have been combined, and they have been used together with cell therapy or controlled release chemical compounds. This double function has driven them as potential candidates for the chronic treatment of IS. In fact, the most developed are in different phases of clinical trial. In this review, we will show the ischemic scenario and address the most important criteria to achieve a successful neuroreparation from the point of view of biomaterials. The spontaneous processes that are activated and how to enhance them is one of the keys that contribute to the success of the therapeutic approach. In addition, the different routes of administration and how they affect the design of biomaterials are analyzed. Future perspectives show where this broad scientific field is heading, which advances every day with the help of technology and advanced therapies.

Molecular and Pharmacological Modulation of CALHM1 Promote Neuroprotection against Oxygen and Glucose Deprivation in a Model of Hippocampal Slices.

Calcium homeostasis modulator 1 (CALHM1) is a calcium channel involved in the regulation of cytosolic Ca2+ levels. From a physiological point of view, the open state of CALHM1 depends not only on voltage but also on the extracellular concentration of calcium ([Ca2+]) ions. At low [Ca2+]e or depolarization, the channel is opened, allowing Ca2+ influx; however, high extracellular [Ca2+]e or hyperpolarization promote its resting state. The unique Ca2+ permeation of CALHM1 relates to the molecular events that take place in brain ischemia, such as depolarization and extracellular changes in [Ca2+]e, particularly during the reperfusion phase after the ischemic insult. In this study, we attempted to understand its role in an in vitro model of ischemia, namely oxygen and glucose deprivation, followed by reoxygenation (OGD/Reox). To this end, hippocampal slices from wild-type Calhm1+/+, Calhm1+/-, and Calhm1-/- mice were subjected to OGD/Reox. Our results point out to a neuroprotective effect when CALHM1 is partially or totally absent. Pharmacological manipulation of CALHM1 with CGP37157 reduced cell death in Calhm1+/+ slices but not in that of Calhm1-/- mice after exposure to the OGD/Reox protocol. This ionic protection was also verified by measuring reactive oxygen species production upon OGD/Reox in Calhm1+/+ and Calhm1-/- mice, resulting in a downregulation of ROS production in Calhm1-/- hippocampal slices and increased expression of HIF-1α. Taken together, we can conclude that genetic or pharmacological inhibition of CALHM1 results in a neuroprotective effect against ischemia, due to an attenuation of the neuronal calcium overload and downregulation of oxygen reactive species production.