HSPB2 facilitates neural regeneration through autophagy for sensorimotor recovery after traumatic brain injury.

Autophagy is a promising target for promoting neural regeneration, which is essential for sensorimotor recovery following traumatic brain injury (TBI). Whether neuronal heat shock protein B2 (HSPB2), a small molecular heat shock protein, reduces injury and promotes recovery following TBI remains unclear. In this study, we demonstrated that HSPB2 was significantly increased in the neurons of a TBI mouse model, patients, and primary neuron cultures subjected to oxygen/glucose deprivation and reperfusion treatment. Upon creating a tamoxifen-induced neuron-specific HSPB2 overexpression transgenic mouse model, we found that elevated HSPB2 levels promoted long-term sensorimotor recovery and alleviated tissue loss after TBI. We also demonstrated that HSPB2 enhanced white matter structural and functional integrity, promoted central nervous system (CNS) plasticity, and accelerated long-term neural remodeling. Moreover, we found that autophagy occurred around injured brain tissues in patients, and the pro-regenerative effects of HSPB2 relied on its autophagy-promoting function. Mechanistically, HSPB2 may regulate autophagy possibly by forming the HSPB2/BCL2-associated athanogene 3/sequestosome-1 complex to facilitate the clearance of erroneously accumulated proteins in the axons. Treatment with the autophagy inhibitor chloroquine during the acute stage or delayed induction of HSPB2 remarkably impeded HSPB2's long-term reparative function, indicating the importance of acute-stage autophagy in long-term neuro-regeneration. Our findings highlight the beneficial role of HSPB2 in neuro-regeneration and functional recovery following acute CNS injury, thereby emphasizing the therapeutic potential of autophagy regulation for enhancing neuro-regeneration.

Dissecting the neurovascular unit in physiology and Alzheimer's disease: Functions, imaging tools and genetic mouse models.

The neurovascular unit (NVU) plays an essential role in regulating neurovascular coupling, which refers to the communication between neurons, glia, and vascular cells to control the supply of oxygen and nutrients in response to neural activity. Cellular elements of the NVU coordinate to establish an anatomical barrier to separate the central nervous system from the milieu of the periphery system, restricting the free movement of substances from the blood to the brain parenchyma and maintaining central nervous system homeostasis. In Alzheimer's disease, amyloid-ß deposition impairs the normal functions of NVU cellular elements, thus accelerating the disease progression. Here, we aim to describe the current knowledge of the NVU cellular elements, including endothelial cells, pericytes, astrocytes, and microglia, in regulating the blood-brain barrier integrity and functions in physiology as well as alterations encountered in Alzheimer's disease. Furthermore, the NVU functions as a whole, therefore specific labeling and targeting NVU components in vivo enable us to understand the mechanism mediating cellular communication. We review approaches including commonly used fluorescent dyes, genetic mouse models, and adeno-associated virus vectors for imaging and targeting NVU cellular elements in vivo.