No abstract

The anti‐apoptotic Bcl‐xL is a promising agent to prevent neurodegeneration in Parkinson’s disease, which is characterized by a demise of dopaminergic neurons. We linked Bcl‐xL to a peptide that allows its delivery across biological membranes and the blood–brain barrier. We tested the fusion protein in two models of Parkinson’s Disease. Cell‐permeable Bcl‐xL protected neuroblastoma cells from the selective neurotoxin 1‐methyl‐4‐phenylpyridinium. Furthermore, its systemic application in aged mice protected dopaminergic neurons following administration of MPTP as revealed by counting of tyrosine hydroxylase‐immunoreactive neurons in the substantia nigra pars compacta. Hence, we present that a cell‐permeable form of an anti‐apoptotic protein can be delivered to CNS neurons through its systemic application, and we provide the proof that the delivery of this protein to the CNS neurons effectively prevents neuronal cell death in models of chronic neurodegenerative diseases.

BackgroundCharacterisation of anatomical distribution and the clinical impact of middle cerebral artery M2 (MCA-M2) segment occlusion and its subsequent cortical branches (CBs) in acute ischaemic stroke patients (AIS).MethodsRetrospective, monocentric study analysing radiological and clinical data of AIS patients with MCA-M2 segment occlusion with regard to the anatomic distribution of MCA-M2 occlusion and its subsequent CB.ResultsA total of 203 patients (median age 77 (IQR 66–83) years, 112 women) were included. There was an equal distribution of right-sided versus left-sided MCA-M2 vessel occlusions (right: n=97; left: n=106), as well as with a median number of affected MCA-M2 CBs of 4 (IQR, 3–6) and a median National Institute of Health Stroke Scale score (NIHSS) on admission of 9 (3–15). For both hemispheres, CBs of the inferior trunks were significantly more affected than the superior trunks. Endovascular treatment (EVT, n=94) was associated with a significant better outcome compared with patients with medical management alone (p=0.027).ConclusionIn acute MCA-M2 segment occlusions, inferior trunks are significantly more affected compared with the superior trunks. The subsequent CBs of the paracentral region of both hemispheres are more commonly involved. In eloquent vascular territories, EVT was more often performed.