Human adipose-derived stem cells (huADSC) were generated from fat tissue of a 65-year-old male donor. Flow cytometry and reverse transcription polymerase chain reaction (RT-PCR) analyses indicated that the huADSC express neural cell proteins (MAP2, GFAP, nestin and β-III tubulin), neurotrophic growth factors (BDNF and GDNF), and the chemotactic factor CXCR4 and its corresponding ligand CXCL12. In addition, huADSC expressed

The endoplasmic reticulum (ER) is an intracellular organelle that performs multiple functions, such as lipid biosynthesis, protein folding, and maintaining intracellular calcium homeostasis. Thus, conditions wherein the ER is unable to fold proteins is defined as ER stress, and an inbuilt quality control mechanism, called the unfolded protein response (UPR), is activated during ER stress, which serves as a recovery system that inhibits protein synthesis. Further, based on the severity of ER stress, the response could involve both proapoptotic and antiapoptotic phases. Intracerebral hemorrhage (ICH) is the second most common subtype of cerebral stroke and many lines of evidence have suggested a role for the ER in major neurological disorders. The injury mechanism during ICH includes hematoma formation, which in turn leads to inflammation, elevated intracranial pressure, and edema. a proper understanding of the injury mechanism(s) is required to effectively treat ICH and closing the gap between our current understanding of ER stress mechanisms and ICH injury can lead to valuable advances in the clinical management of ICH.Cells 2020, 9, 750 2 of 20 because of cardiovascular conditions, with hypertension playing a major role. PBI is characterized by mechanical injury followed by a mass effect with the initial ictus causing physical tissue disruption that then leads to pathophysiological conditions in the brain.A sudden rise in intracranial hematoma volume causes an increase in barotrauma and reduces blood flow to the area of the ictus [4,5]. Typically, PBI is followed by SBI, which is considered as a devastating stage after ICH, and the severity of SBI depends on the rate of recovery and location of the ICH. SBI involves the neuroinflammatory response to the triggering of the coagulation cascade through activation of the immune system. The inflammation size is based on the volume and position of the hematoma [5][6][7]. The various pathological factors responsible for SBI include the host immune response, release of thrombin, release of clot components (iron and heme)

Background: Neuroinflammation is a hallmark in intracerebral hemorrhage (ICH) that induces secondary brain injury, leading to neuronal cell death. ER stress-triggered apoptosis and proteostasis disruption caused neuroinflammation to play an important role in various neurological disorders. The consequences of ER stress and proteostasis disruption have rarely been studied during the course of ICH development. Methods: ICH was induced by collagenase VII-S intrastriatal infusion. Animals were sacrificed at 0, 3, 6, 24, and 72 h post-ICH. Rats were determined for body weight changes, hematoma volume, and neurological deficits. Brain tissues were harvested for molecular signaling analysis either for ELISA, immunoblotting, immunoprecipitation, RT-qPCR, protein aggregation, or for histological examination. A non-selective proteasome inhibitor, MG132, was administered into the right striatum three hours prior to ICH induction. Results: ICH-induced acute proteasome over-activation caused the early degradation of the endoplasmic reticulum (ER) chaperone GRP78 and IκB protein. These exacerbations were accompanied by the elevation of pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP) and pro-inflammatory cytokines expression via nuclear factor-kappa B (NF-κB) signal activation. Pre-treatment with proteasome inhibitor MG132 significantly ameliorated the ICH-induced ER stress/proteostasis disruption, pro-inflammatory cytokines, neuronal cells apoptosis, and neurological deficits. Conclusions: ICH induced rapid proteasome over-activation, leading to an exaggeration of the ER stress/proteostasis disruption, and neuroinflammation might be a critical event in acute ICH pathology.