Neuronal Injury

Characteristics of the CNS - complex interactions

• Neurotransmitters​

• Receptors ​

• Genes ​

• Environment

Characteristics of the CNS - different pathways for damage

• Apoptosis​

• Necrosis​

• Infection​

• Ischemia​

• Trauma - brain and spinal cord​

• Chemical/toxicity​

• Radiation​

• Nutritional deficiency ​

• Genetic influences​

Apoptosis

• Programmed ​

• Not associated with an ​

• Normal process that helps to regulate ​

• This process can be excessive in times of ​

  • Can occur regardless of the _____ of CNS damage

• Increase w/

• Programmed cell death​

• Not associated with an inflammatory response​

• Normal process that helps to regulate overproduction of cells​

• This process can be excessive in times of CNS damage​

  • Can occur regardless of the type of CNS damage

• Increase w/ stroke, result of ischemic processes, neurodegenerative diseases (might be genetic in nature), traumatic injuries, drug related disorders

Necrosis

• Cellular _____​​

• F​

• Cell d_____​

• Release of ​

  • These materials start to encroach on

• Always

• is associated w/

• Cellular swelling​

  • Water enters the cell and causes cell membranes to rupture​

• Fragmentation​

• Cell disintegration ​

• Release of cytotoxic materials​

  • These materials start to encroach on neighboring cells causing damage there

• Always pathological

• is associated w/ an inflammatory response

Comparison of necrosis and apoptosis​

• Necrosis

• Apoptosis

Cell size​

Nucleus​

Plasma membrane​

Cellular contents​

Adjacent inflammation​

Physiologic or pathologic​

• Necrosis

  Enlarged (swelling)​

  Pykinosis  karyorrhexis  karyolysis​

  Disrupted​

  Enzymatic digestion; may leak out of cell​

  Frequent​

  Invariably pathologic (culmination of irreversible cell injury)​

• Apoptosis

Reduced (shrinkage)​

Fragmentation into nucleosome-size fragments​

Intact; altered structure, especially orientation of lipids​

Intact; may be released into apoptotic bodies​

No​

Often physiologic, means of eliminating unwanted cells; may be pathologic after some forms of cell injury, especially DNA damage​

Excitotoxicity

• how the body responds to

• Excitatory _______ _______ ______ are activated ​

• Calcium ions enter cells → activation of ________ ________ → release of _______ → damage to ___________ cells​

• This process leads to _______ _______ _______ (oxidative stress) → _______​

• Increase in oxidative stress is a secondary complication in diseases such as

• how the body responds to necrosis

• Excitatory amino acid receptors are activated ​

• Calcium ions enter cells → activation of intracellular function → release of excitotoxins → damage to neighboring cells​

• This process leads to free radical formation (oxidative stress) → apoptosis​

• Increase in oxidative stress is a secondary complication in diseases such as Alzheimer’s,Parkinson’s, and ALS

Glial cells

• Macroglia (from nerve cells; most populous)- when thinking about neurological disorders that impact the brain tissue directly, most of the time we’re thinking about the impact they have on the microglial cells​

  • Astrocytes​

  • Oligodendrocytes​

  • Schwann cells​

• Microglia (immune cells)

  • immune function

  • modulate inflammatory process

  • have macrophage properties + it will be the release of those materials that will be damaging to the surrounding cells

  • older adults have heightened immune response → may be why we see an increase in prevalence of some neurological diseases such as Alzheimer’s, PD in the older population

Astrocytes

• Most ______ brain cells

  • support ____

  • provide _____ to brain​

• Permeable to _____​

• Monitor and remove _____ and other _____​

• Can seal off ______ brain tissue

• Most numerous brain cells

  • support NS

  • provide nutrition to brain​

• Permeable to potassium​

• Monitor and remove glutamate and other debris​

• Can seal off damaged brain tissue

Damage to astrocytes

• Proliferative ______damage occurs​

• _______, _______ occur ​

• Altered _______ expression in the setting of brain injury​

• Can be a site of ______ which can _______ surrounding ______ tissues and _______ structures

• Proliferative neuronal damage occurs​

• Swelling, scarring occur ​

• Altered genetic expression in the setting of brain injury​

• Can be a site of neoplasm which can compress surrounding neural tissues and vascular structures

Oligodendrocytes and Schwann cells

• Oligodendrocytes = ​

• Schwann cells = ​

• Both help to produce the ​

• Oligodendrocyte function is disrupted in demyelinating diseases such as

• Oligodendrocytes = CNS​

• Schwann cells = PNS​

• Both help to produce the myelin sheath surrounding the axon ​

• Oligodendrocyte function is disrupted in demyelinating diseases such as multiple sclerosis

Neurons (nerve cells)

• DNA mutation can lead to ​

  • Abnormalities to ​

  • Drug ______ or ______

• DNA mutation can lead to vulnerability to neurological disease​

  • Abnormalities to gene structure​

  • Drug toxicity or misuse

Neurotransmission

• Depolarization of terminal causes _______ influx and opens channels in _______ neuron​

• Neurotransmitters are ______ ​

• Drugs will affect this process by

• Depolarization of terminal causes sodium influx and opens channels in postsynaptic neuron​

• Neurotransmitters are released ​

• Drugs will affect this process by blocking transmission, increase or decrease the release of neurotransmitters,allow for reuptake of neurotransmitter back into the presynaptic terminal, or change the properties of the membrane

Recovery from neurological injury​- Peripheral nerve injury

• New​

• Proliferation of ​

• Microsurgical approximation may result in

• New axonal sprouts​

• Proliferation of Schwann cells​

• Microsurgical approximation may result in reinnervation

Neuroplasticity

• Redistribution of ​

• Alterations of ​

  • N______​

  • I_____ S_____​

  • R______

• Redistribution of cortical mapping​

• Alterations of neural networks​

  • Neurotransmitters​

  • Individual synapses​

  • Receptors

Factors that influence recovery

• ________ of the lesion

• _______ of the lesion​

• Is the injury ______ or _______?​

• Was the injury _______ or _______​

• A____

• E_____

• B____ ____​​

• E______ r_________

• Location of the lesion

  • damage to brainstem will have devastating effects​

• Size of the lesion​

• Is the injury static or progressing?​

• Was the injury sudden (massive hemorrhage) or gradual (slow growing tumor)?​

• Age

  • older adults do not have the capacity to heal as much as younger populations​

• Environment

  • are they being appropriately stimulated in being asked to perform tasks that are going to help promote neuroplasticity​

• Brain health​

  • Blood flow​

  • Immune systems​

  • Metabolism ​

• Emotional regulation