2/24/15 – lecture 12 – Brain Injury: Tumors, Infection, Stroke, and Trauma- REMEMBERo You don’t need a brain to learn and remembero You don’t need to be consciously aware to learn and remembero There’s no time limit on learning and remembering- If memory is so important and biologically regulated, how come we remember so much stupid stufo Age: we are better able to consolidate, store and recall information when we are youngero Repetition: things that we are repeatedly exposed to activate learning mechanisms like LTP and synaptogenesis even if they’re unimportanto Emotion: high levels of emotions (good or bad) can enhance memoryo Sleep: good, sufficient, restful sleep enhances memory - Goal: to learn what causes damage to the brain or nervous system and how the nervous system repairs or adapts to the damage- What is brain Damage?o The damage or death of neurons due to injury or other insults Neurons can die by either necrosis or apoptosis- Necrosis: “accidental cell death”, a death that the cell doesn’t see comingo Does not require signaling and gene expressiono Characterized by the swelling of cells and the bursting/lyses of the cell Ends up causing inflammation to try and get rid of the cell debriso OFTEN represents the most immediate consequences of a brain damaging even- Apoptosis: “cell suicide”, regulated form of cell deatho Requires signaling and gene expressiono Characterized by the cells shrinking and then separating into apoptotic bodies and then absorbed by other cells No inflammation because they are tiny and neato SECONDARY consequences occurring hours or days after the initial brain damaging event- Brain damaging events -> Necrosis often comes first (cells die almost immediately) -> Apoptosis follows second (cells are damaged but didn’t entirely die so they commit suicide)o Causes of Brain Damage Cerebrovascular Disorders: a group of brain dysfunctions related to disorders of the blood vessels supplying the brain- Aneurysms and Cerebral Hemorrhage: weakening and eventual bursting of a blood vessel and seepage of blood into brain areas around it, caused by high blood pressure- Thrombus and Cerebrovascular Occlusion: blockage of a cerebral artery, cutting of oxygen and nutrient delivery, often caused by atherosclerosis, a disease in which excess fats in the diet are deposited into blood vesselso Mechanisms by which neurons die in Cerebrovascular Disorders Crushing and compression of neurons by bleeding and hematoma: causes death by necrosis, occurs in cerebral hemorrhage only Hypoxia: lack of oxygen in “downstream” neurons due to lack of blood flow, caused by both necrosis and apoptosis, occurs in both cerebral hemorrhage and cerebrovascular occlusion- Necrosiso Energy deficit: lack of oxygen disrupts energy productiono Lactic acidosis: (not very efficient) buildup of lactic acid from anaerobic metabolism, low pH kills cells- Apoptosiso Oxidative Stress: buildup of metabolic intermediates due to abnormal ATP production in the absence of oxygen that damage DNA, proteins, and membraneso Glutamate Excitotoxicity: hypoxic neurons release excess amounts of the neurotransmitter glutamate,which causes huge Ca2+ influx into post synaptic neurons, triggering apoptosiso Inflammation: immune cells can also accidentally damage and kill neurons by releasing substances that trigger apoptosis DOESN’T cause inflammation, inflammation CAUSES apoptosis Brain Tumors: Large, excessively proliferating masses of cells in the brain or spinal chord (children and adults and how aggressive?)- Glioma: glial cell tumor, VERY aggressive, often found in ADULTS- Secondary Metastases: tumors that form elsewhere in the body and invade into thebrain from the bloodstream, VERY aggressive, typically found in ADULTS- Primitive Neuroectodermal Tumor (PNET): VERY aggressive neuroblastic tumor in YOUNG KIDS, 50% survival rate- Meningioma: tumor of the meninges that grow outside the brain, typically very SLOW growing, typically found in ADULTSo Neural Changes and Brain Tumors Necrosis- Compression due to tumor growth: crushes and kills neurons by necrosis, also causes neuronal misfiring Necrosis and Apoptosis- Compression of blood vessels due to tumor growth: occludes blood supply, can cause hypoxia and death of neurons by necrosis and apoptosis- Tumor hijacking of blood supply of nutrients and oxygen: can cause hypoxia and death of neurons by necrosis and apoptosis Apoptosis- Inflammation: immune cell attacking tumor release substances that cause neurons to die by apoptosis Physical Trauma/ Traumatic Brain Injury (TBI)- Causes of TBI?o Sports, car accidents, falling, assaults, military injuries, and abuse (in children.. hit, shaken baby syndrome, etc)- Sources of Injury in TBIo Coup: the initial injury to the brain form the skull striking an objecto Contrecoup: the “rebound” injury to the opposite part of the brain caused when the brain reboundso Hematoma: tearing of blood vessels resulting in leakage of blood into the braino Edema: swelling of the brain tissue in response to trauma- How do Neurons Die with TBI?o Necrosis Primary Brain Injury: necrosis of neurons due to physical damage ofneurons due to coup, contrecoup, hematoma and edemao Necrosis and Apoptosis Compression of blood cessels due to hematoma: occludes blood supply to the brain, causing hypoxia Decreased blood supply due to tearing of blood vessels: can cause hypoxiao Apoptosis Inflammation: immune cells removing cell debris release substances that cause some surviving neurons to die by apoptosis Infections: infection of the brain by microorganisms- 2 Main Types of Infectious Organisms = Bacteria and Viruseso Bacterial Brain Infections Bacterial Meningitis: invasion of the meninges by one of several diferent species of bacteria Syphilis: sexually transmitted bacterial diseaseo Viral Brain Infections Rabies: infects nerves through bites to the skin and moves into the Central Nervous System Polio: infects GI tract but can enter Central Nervous System and infect sensory and motor neurons and cause paralysis- Neural Changes in Brain Infectionso Necrosis Primary Injury: necrosis of neuronal cells by viral lysis or bacterial toxino Apoptosis Secondary injury: immune system tells infected neurons to die by apoptosis Drugs and Neurotoxins: destruction of neural tissues by ingested toxic substances- Sources of common Neurotoxic Substanceso