Assoc. Prof. MUDr. Markéta Bébarová, Ph.D. Department of Physiology, Faculty of Medicine, Masaryk University Brain and behavior,  environment of the neuron This presentation includes only the most  important terms and facts. Its content by  itself is not a sufficient source of information required to pass the Neuroscience exam.  Figures and tables re‐used from: ‐ Principles of Neural Science (5th ed.), Kandel et al. (2013) ‐ Medical Physiology (2nd ed.), Boron and Boulpaep (2012) ‐ Neuroscience (4th ed.), Purves et al. (2008) ‐ Medical Neurobiology (1st ed.), Mason (2011) ‐ Review of Medical Physiology (20th ed.), Ganong (2005) ‐ Atlas of Human Physiology (6th ed.), Silbernagl a Despopoulos (2004) Functional regions of the CNS Functional regions of the CNS Functional regions of the brain cortex Broadmann 52 areas Methods for measurement of regional cerebral blood flow, thus, of brain activity PET (positron emission tomography) - a substance labelled by radionuclides with a short half time - the substance is injected, the increase and following decrease of its concentration is evaluated by scintillation detectors placed around the head - e.g. labelled 2-deoxyglucose – its consumption is a good indicator of the flow Functional regions of the brain Functional regions of the brain fMRI (functional magnetic resonance) - better resolution - reduced haemoglobin becomes paramagnetic, change the signal emitted by blood, we can measure the amount of oxyand deoxyhaemoglobin as an indicator of the blood flow Functional regions of the brain Methods for measurement of regional cerebral blood flow, thus, of brain activity Functional regions of the brain Homeostasis • is the process of ensuring that bodily variables stay  within a preferred range • endocrine, nervous, immune systems Homeostasis – nervous system • brain is „smart“ – when possible anticipate challenges to homeostasis → all an cipatory  homeostatic adjustments require intact forebrain (voluntary reaction) • unexpected challenges to homeostasis → met by  largely unconscious reflexes mediated by the spinal  cord and/or brainstem Homeostasis – nervous system • interactions with external environment require  behavioural component as a function of the brain • behaviour (from simple to complex) requires  contribution of three main components: sensory, executive, motivational Goal directed behaviour • energetic balance • volume and osmolarity • temperature • performance • strenghthen health • reproduction • defense • ........... Neuron • approx. 1011 of nerve cells (glial cells 10 times frequent) • the most consistent neuronal trait ‐ individuality • neurons differ in location, morphology, connections,  physiological characteristics • cells within localized clusters (nuclei) or layers (laminae)  often share many common characteristics Most neurons share a group of traits:  • derive from ectoderm • four morphological regions – dendrites, body, axon,  synaptic terminals Most neurons share a group of traits:  • four functional components – input, integrative,  conductile, output • generate electrical potentials • communication with another neurons Neuron The law (doctrine) of dynamic polarization:  Neuronal information flows in one direction  from the  dendrites and the soma to the axon and synaptic  terminals. (Cajal) Glial cells • CNS ‐ oligodendrocytes, astrocytes, microglial cells • PNS ‐ Schwann cells • critical for development of NS CNS PNS Myelin Myelin insulates axons – rapid (saltatory) conduction of AP. demyelination Astrocytes • metabolic functions: K+, pH, oxidative stress (GSH),  energy storage (glycogen), glutamate‐glutamin shuttle • modulation of synaptic activity, tissue repair Cerebral Compartments Ganong´s Review of Medical Physiology, 23rd edition Cerebral Circulation Cerebral Circulation • provides: 1) constant sufficient blood supply 2) dynamic blood redistribution (metabolic hyperaemia) (black-out during several seconds of the brain ischemia, irreversible damage during several minutes) Cerebral Circulation • Anatomical specialities of cerebral circulation: 1) circulus arteriosus cerebri (interconnection of main cerebral arteries by anastomoses) (almost 1/2 of the vasal resistance falls on arteries which are abundantly innervated) 3) very short arteriols 2) very high density of capillaries (3000 – 4000 capillaries / mm2 od the grey matter)  minimalization of diffuse distance for gases and other substances Cerebral Circulation • Functional adaptation of cerebral circulation: 4) high reactivity on changes of CO2 concentration 1) high and stable blood flow 2) high O2 extraction 3) well developed autoregulation (myogenic and metabolic) 5) local vs. total hypoxia 6) innervation Cerebral Circulation Ganong´s Review of Medical Physiology, 23rd edition. sympathetic system Cerebral Circulation • Special physical conditions of cerebral circulation: 1) solid cover of brain by skull Monro-Kelli theory  flow may be increased only by acceleration of the blood flow, not by an increase of capacity of the bloodstream  Cushing reflex 2) gravity orthostatic reaction (postural syncope) Cerebral Circulation Ganong´s Review of Medical Physiology, 23rd edition • Blood-brain barrier cerebral capillaries – tight inter-endothelial connections Cerebral Circulation • Blood-brain barrier  lipophilic substances (O2, CO2, xenon; unbound forms of steroid hormones) By free diffusion:  water (aquaporins; osmolality of blood and cerebrospinal fluid is identical!)  ions (e.g. H+, HCO3- vs. CO2 !) By transcellular transport (regulated):  glucose – the main source of energy for neurons (free diffusion would be slow – accelerated by GLUT)  transporters for thyroid hormones, some organic acids, choline, precursors of nucleic acids, aminoacids, … Cerebral Circulation • Blood-brain barrier • Functions: - maintenance of constant composition of the neuron environment - protection of brain against endogenic and exogenic toxins - prevention of loss of neurotransmitters to the bloodstream Cerebrospinal fluid - production - rate of production: 450‐550 ml/day  (70 % come from plexus choriodei) circulating volume:  130‐150 ml CSF pressure in supine position in  lumbar region:  70‐180 mmH2O Cerebrospinal fluid - composition - Cerebrospinal fluid - circulation Cerebrospinal fluid ‐ function • mechanical and protective • drainage • homeostatic • information transfer  Cerebrospinal fluid ‐ function • mechanical and protective • drainage • homeostatic • information transfer  Cerebral Circulation • Paraventricular organs  brain regions where the blood-brain barrier is missing (fenestrated capillaries) Ganong´s Review of Medical Physiology, 23rd edition - secretion of polypeptides (oxytocin, vasopressin, …), - chemoreceptive zones (AP) - osmoreceptive zones (OVLT) Blood flow in brain ‐ methods • global: Fick principle ‐ Kety method using inhaled nitrous  oxide (N2O) • Perfusion CT • Invasive methods (local monitoring in neurosurgery): flow: probe with thermistors  pO2  • magistral arteries ultrasound • transcranial Doppler ultrasound • PET, fMRI Energy sources • glucose (does not need insulin) astrocytes GLUT 1 (→ lactate) neurons GLUT 3 • under some conditions also: ketone bodies: starvation and diabetes • new‐borns also FFA during breastfeeding Energy sources • most of the energy is needed to maintain ion  gradients across cell membranes and transmit  electrical impulses • part of glucose in neurons is converted to amino  acids and lipids • part of the total glucose is utilised by glial cells Ammonium • glutamate entering the brain takes up ammonia and  leaves as glutamine → opposite to the reac on of kidney • ammonium is very toxic for neural tissue • hepatic encephalopathy