Cugota Canals, Roger

Universitat Autònoma de Barcelona. Facultat de Biociències

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Red lines in the ischemic neurovascular unitEstablishing the neurovascular unit’s chronology in ischemic stroke’s onsetCugota Canals, RogerBachelor’s degree final project – Bachelor’s degree in Biomedical SciencesFacultat de biociències, Universitat Autònoma de BarcelonaThe main aim of this project is to establish an approximate chronology ofthe different physiological, tissular and cellular events which take place inthe neurovascular unit within the situation of an ischemic stroke.I. CONTEXT AND INTRODUCTION II. AIMSCONCLUDING REMARKSIn this review project either most recent publications or classical onesrelated to the neurovascular unit and its response to ischemia werestudied:• Firstly a search of terms neurovascular, ischemic stroke andendothelial responses was held in Pubmed and ScienceDirect, and thearticles found were ordered by preference and impact.• Secondly the articles considered most relevant or important were readand summarized and their bibliography extensively analyzed.• Eventually a graphical representation of neurovascular unitimplications in ischemic stroke was made in order to summarize allthe information found.III. MATERIALS AND METHODS The term Stroke or cerebrovascular accident refers to the sudden death ofa cerebral tissue area due to lack of oxygen when the blood flow to thebrain is impaired by blockage or rupture of a cerebral artery. According to the World Health Organization data, stroke is the secondcause of death worldwide, being responsible approximately of the 12% ofworldwide deaths every year. In Pathology field, different types of stroke are defined according to itcauses or consequences:• Hemorrhagic stroke ‐> Vessel rupture inside the Central Nervous System.• Ischaemic stroke ‐> Blockage of cerebral blood flow or oxygen supply tothe brain. Ischemic stroke subtypes are summarized in the followingschema:IV. NEUROVASCULAR UNIT AND ITS RESPONSE TO ISCHAEMIANeurovascular unit (NVU) (concept) derives of a big number ofobservations which reported how vascular elements, supportingcompounds and neuronal cells work together in order to achievethe complete protection and metabolic regulation that brain needsat any time.The diagram below illustrates different cellular elements interacting with endothelium in the normal NVU.  Every one of those elements is capable of regulating endothelium physiology in the NVU by releasing a wide range of metabolic mediators, even though in normal conditions only astrocyte and pericyte influences are remarkable. The NVU suffers changes and find its physiology perturbed from the veryonset of ischemic situation. As a result of the research that has beendone, all changes that NVU suffers due to ischaemia can be classifiedunder the next four main tittles:1. Loss of endothelial permeability barrier leading to perivascular edemaestablishment .2. Loss, by enzymatic digestion, of the vessel basal lamina andextracellular matrix, leading to haemorrhagic transformation process.3. Alterations in cell‐matrix signaling systems, which would start a widerange of cytological changes as iniciating apoptosis‐like cell deathpathways.4. Leukocyte adhesion receptors expression in endothelial surface ,leading to neuroinflamation processes.Neurovascular crhonology after ischaemia onset Fig.2. Schematic representation of cell interaction in  the neurovascular unit. Cellular elements are shown in yellow,endothelium in red, immune system inorange, basal lamina in grey and extracellularmatrix in blue. An interaction is more frequentas more overlapped are the circles.Infograhy by the author.As a result of the present study, a graphic representation of the chronology  of neurovascular unit processes promoted by ischaemia has been made:Fig.3.Graphic representation of ischaemia chronology in the neurovascular unit. Different colours show implication of different nature compounds in the neurovascular unit and its surrounding tissue.  Infography by the author.Fig.1. Characteristics of cerebral microvessels under normoxic conditions. Left picture: Depictionof neurovascular unit displaying relationships between neurons and their supply capillaries.Right picture: Capillary from rat inferior colliculus. Note endothelial cell, basal lamina matrix, andsurrounding astrocyte end‐foot. 4.5‐5.0 µm diameter. Adapted from del Zoppo and Hamann, 2011.CREDITS FROM FIGURES:Figure 1: Del Zoppo, G. J., & Hamann, G. F. (2011). The Cerebral Microvasculature and Responses to Ischemia. Stroke (Fifth Edit.). Elsevier. doi:10.1016/B978‐1‐4160‐5478‐8.10002‐8Figures 2 and 3: Infography by the author. Neurovascular unit experiments alterations from the very instant that ischaemia is established. The neurovascular unit disengagging is the most clear red line in ischaemic stroke, leading to the start of infarction andirreversible tissue injury.  New pharmacological strategies should target the basal lamina of cerebral capillaries in order to protect it from digestion.

Red lines in the ischemic neurovascular unit : estabishing the neurovascular unit's chronology in ischemic stroke's onset

http://ddd.uab.cat/pub/tfg/2015/143509/TFG_rogercugotacanals.pdf

Red lines in the ischemic neurovascular unit : estabishing the neurovascular unit's chronology in ischemic stroke's onset

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