Neurosicience development of the neurvous systems coursepack

Neuroscience Development of the Nervous System Thomas J Cusack, M.D., M.S Barrow Neurologic Institute Development of the Nervous System Gastrulation (week 3) • primary germ layers • Ectoderm • Mesoderm • Endoderm • Ectoderm • Neuroectoderm • Neural crest cells NEURO01_01_ Germ Layer Derivatives NEURO01_01_ Neural Plate Development • Neuroectoderm → CNS and PNS • Notochord induces neural plate development • Notochord remnant in adults→ nucleus pulposus • Neural tube closes • Neural crest cells develop NEURO01_01_ Neurulation Neurulation (week 3) • Sensory (alar) plate • Dorsal nerve roots • Motor (basal) plate • Ventral nerve roots • Dorsal and ventral roots join to form spinal nerves NEURO01_01_ Neural Tube Pathogenesis NEURO01_01_ Neuroscience Central Nervous System Divisions Thomas J Cusack, M.D., M.S Barrow Neurologic Institute Development of the Nervous System NEURO01_02_ Telencephalon Cerebral hemispheres Basal ganglia (most) Lateral ventricles Diencephalon Thalamus Hypothalamus Subthalamus Epithalamus Retina Optic nerves Third ventricle Mesencephalon Midbrain Cerebral aqueduct Metencephalon Pons Cerebellum Fourth ventricle Myelencephalon Medulla Fourth ventricle Neural Tube Defects Condition Anencephaly Description • • • • • • Example Failure of anterior neuropore to close Brain does not develop Incompatible with life ↑ serum and amniotic fluid AFP ↑ acetylcholinesterase Polyhydramnios Anencephaly, commons.wikimedia.org • Holoprosencephaly • • • Incomplete separation of the cerebral hemispheres One ventricle in telencephalon Seen in trisomy 13 (Patau syndrome) Associated craniofacial malformations Alobular_holoprosencephaly.wikimedia.org NEURO01_02_ Spina Bifida • Spina bifida occulta • • • Failure of posterior neuropore to close, or to induce bone growth around it Vertebrae fail to form around spinal cord No increase in AFP Asymptomatic; tuft of hair over defect Spina bifida with meningocele • • Meninges protrude through vertebral defect Increase in AFP • • Meninges and spinal cord protrude trough vertebral defect; seen with Arnold- Chiari type II Increase in AFP • • • Most severe Spinal cord can be seen externally Increase in AFP Spina bifida with meningomyelocele Spina bifida with myeloschisis Kaplan Anatomy Table IV-I-3 NEURO01_02_ Inhaled Anesthetics Specific Side Effects • • • • • Halothane: hepatotoxic Methoxyflurane: nephrotoxic Enflurance: proconvulsant Nitric oxide: diffusional hypoxia, spontaneous abortions All (except nitric oxide): ↑ risk for malignant hyperthermia NEURO11_07_ Malignant Hyperthermia Clinical presentation • Muscle rigidity, hyperthermia, hypertension, acidosis, hyperkalemia • Also associated with skeletal muscle relaxant use Etiology • Affected patients thought to be genetically predisposed • Carry mutations in genes encoding ryanodine receptors and/or skeletal muscle L-type calcium channels Treatment • Dantrolene NEURO11_07_ Barbiturates Characteristics • Example: thiopental • Use for induction of anesthesia • Highly lipid soluble → rapid CNS entry and onset • Short acting due to rapid distribution into tissues/fat • Prolongs GABA activity Side effects • ↓ cerebral blood flow NEURO11_07_ Benzodiazepines Characteristics • Example: midazolam • Use for sedation and induction of anesthesia • Potentiates GABA via benzodiazepine (BZ1) receptors • ↑ frequency of Cl- channel opening Side effect • Respiratory depression, hypotension, amnesia NEURO11_07_ Propofol Characteristics • Use for induction and maintenance of anesthesia • Potentiating GABA activity • Associated with less postoperative nausea than thiopental Side effects • Cardiac depression NEURO11_07_ Opioids Drugs in class • Morphine, fentanyl, codeine, methadone, meperidine Mechanism of action • Opioid receptor agonist • Four major opioid receptors: mu, kappa, delta, OFQ/N • Endogenous opioid receptor agonists (enkephalins, dynorphins, endorphins) • Regulate pain, stress, temperature, respiration, endocrine activity, mood, motivation, and GI activity NEURO11_07_ Exogenous Opioid Receptor Agonists Characteristics • Primarily act upon central and peripheral mu and kappa receptors • Used with CNS depressants for surgeries Side effects • Respiratory depression Butophanol • Mechanism: mu receptor partial agonist and kappa receptor agonist • Use for severe pain • Side effects: less respiratory depression than full opioid agonists NEURO11_07_ 10 Ketamine Characteristics • Dissociative anesthetic Mechanism • NMDA-receptor antagonist • Use for induction of anesthesia Side effects • Altered mental status upon reawakening • Cardiovascular stimulation • ↑ intracranial pressure NEURO11_07_ 11 Local Anesthetic Classification Two types • Esters • Procaine, cocaine, benzocaine, and tetracaine • Amides • Lidocaine, mepivacaine, bupivacaine Note Esters have one “I” in their names Amides have > “I” in their names NEURO11_07_ 12 Local Anesthetic Mechanism of Action Mechanism • Blocks inactivated Na1+ channels → slows post potential nerve recovery • Myelinated nerves Order of sensory loss • Pain → temp → touch → pressure Kaplan Pathology Figure IV-4-2 NEURO11_07_ 13 Local Anesthetic Side Effects • Often co-administered with α1 blocker • ↓ absorption into systemic circulation (↓ toxicity) • Prolongs local affect Side effects • Neurotoxicity, cardiovascular toxicity, allergic reaction Other characteristics • ↓ efficacy in acidic tissue (e.g abscesses) NEURO11_07_ 14 Neuroscience Skeletal Muscle Relaxants Thomas J Cusack, M.D., M.S Barrow Neurologic Institute Skeletal Muscle Relaxants Characteristics • Used to induce immobility in surgery and/or ICU • Works at neuromuscular junction nicotinic Ach receptors Depolarizing agents • Example: succinylcholine • Non-competitive nicotinic agonists → induces sustained contraction preventing further contraction • Two phases • Phase I: sustained contraction (fasciculations seen) • Phase II: repolarized yet desensitized myocytes • AChE inhibitors potentiate phase I and overcome effect on phase II NEURO11_08_ Depolarizing-Nondepolarizing Muscle Relaxants Depolarizing agents • Short acting (metabolized by pseudocholinesterase) • Side effects • Hypercalcemia, hyperkalemia, ↑ risk for malignant hyperthermia Non-depolarizing agents • Example: atracurium, vecuronium, rocuronium, mivacurium • Competitive nicotinic agonists • Effect reversible with cholinesterase inhibitors NEURO11_08_ Central Acting Muscle Relaxants Characteristics • Benzodiazepines and baclofen Mechanism • Benzodiazepines act upon GABAA receptors • Baclofen acts upon GABAB receptors • Used in muscle spasticity NEURO11_08_ ... Malformation • Failure of foramina of Lushka and Magendie to open → dilation of 4th ventricle • Agenesis of cerebellar vermis and splenium of the corpus callosum Excessive CSF and destruction of cerebellum... displacement of cerebellar tonsils through foramen magnum Type II • More often symptomatic • Downward displacement of cerebellar vermis and medulla through foramen magnum • Compression of fourth... cells of nervous system • Capable of cell division Astrocytes • Most numerous CNS glial cell type • Many radiating processes • Large bundle of intermediate filaments • Structural support of CNS