Central Nervous System

What does structure dictate?

function

common misconceptions of the CNS

• we only use 10% of our brain

• our brains are supercomputers

  • analog not digital

• listening to classical music increases intelligence

• there is a discrete limit to the memories that can be stored

  • brain has the storage capacity of at least 2.5 × 10¹⁸ bytes

• male and female brains process data differently

operation design

definition

systematic approach

• planning and structuring complex operations

• identification and understanding

  • problem? environment? stakeholders? desired end state?

• feedback

steps of CNS response

• sensory input

• repeated stakehold modification

• final output

operational design conditions

• sense the internal and external environment

  • sensitivity

  • differentiation types of sensory data

• both specific and general control of cell activities

  • one or multple systems?

  • systems overlapping function or structure

• control ranges from very fast (ms) to hours, days or weeks

• must happen at cellular level

What is the organization of the CNS

hierarchal (top down)

structural and functional stratification of CNS

• neuronal language

• neurons controlling the same process must be in the same anatomical space

• neurons controlling cells must demonstrate topographical neuron organization

What must the CNS demonstrate

plasticity

What must the CNS be chemically separated from?

blood to regulate what reaches brain tissues

What is the CNS protected by?

bone and connective tissue

CNS

• brain and spinal cord

• physically separate from PNS by BBB

afferent neurons

inward axonal projections

efferent neurons

outward axonal projections

CNS composition

• 10% neurons making up 50% of the volume

• 90% neuroglia making up the other 50% of the volume

nuclei

collection of neuronal cell bodies with the same function in the same physical space

tunneling nanotubes

membrane projections connecting neurons

gray matter

neuronal cell bodies

white matter

axonal projections

ganglia

collection of neurons with the same function in the same physical space outside the CNS

circuits

anatomical and functional connections between neurons

multipolar neurons

common CNS neuron with a single axon and short dendrites

pyramidal neurons

common, largest CNS neurons multiple long axons and dendrites

neuroglia

non-neuronal cells within the CNS

cranial bones

provide physical protection against mechanical forces

meninges

• multiple connective tissue layers that cover the CNS

• three layers

  1. dura mater

  2. arachnoid mater

  3. pia mater

dura mater

• “Tough mother”

• two fibrous layers

• space between the layers is filled with blood vessels, extracellular fluid, lymphatic vessels

subdural space

between the dura mater and the arachnoid spaces

duro venous sinus

drainage systems allowing the CSF to reenter the blood

subdural hematoma

• physical trauma leads to bleeds onto the brain surface i

• increased fluid presence leads to neuronal cell damage

• MRI used to identify it

arachnoid mater

• “Spiderlike mother”

• epithelial layer

• does not follow the brain’s underlying sulci (furrow) or gyri (smaller ridge or cleft)

subarachnoid space

between the dura and the pia mater

arachnoid villi

move through venous sinuses allowing CSF to exit subarachnoid spaces

pia mater

• “Gentle mother”

• directly on the surface of the brain

• accompanies branches of the cerebral blood vessels

• coverage and protection of CNS tissue and blood vessels containing CSF

meningitis

• viral/bacterial infection leading to pia mater inflammation

• causes severe headaches

• all college students need to be vaccinated against this

vascularization of CNS

• constant 15-20% of cardiac output

• internal carotid and vertebral arteries

  • multiple paths

  • chokehold

• internal jugular veins

anastomose

fusion of blood vessels

Circle of Willis

• alternative paths for blood flow in the brain

• ensures blood supply in face of blockages

brain interstitial system

• fluid-filled space between neurons and capillaries

  • ISF and extracellular matrix

  • 15-20% of total brain volume

  • not equivalent to ISF outside the CNS

• immediate environment surrounding neurons

• highly regulated

origins of brain ISF

CSF and blood vessels

blood brain barrier (BBB) composition

• capillary endothelial cells with tight junctions

• basal lamina

• astrocytic end feet (control point)

• pericytes (angiogenesis and release paracrine signals to induce tight junction formation)

BBB features

• highly selective permeability

• limited paracellular path

• control of ISS

neurovascular unit (NVU)

• composition

  • capillary endothelial cells

  • pericytes

  • astrocytes, microglia

  • neurons

• function

  • regulation of blood flow and BBB

Describe the transport capacity of the BBB

• it has a limited transport capacity

• carrier-mediated

• receptor-mediated

carrier-mediated

• selective and saturable

  • includes amino acids, glucose, nucleotides, small proteins

receptor mediated

• binding and internalization

  • includes hormones, growth factors, enzymes, small proteins

CSF access

• involves hydrophobic diffusions

  • very fast, within secs (10 secs)

  • favorable to fats/lipid soluble molecules (ethanol, THC, nicotine, propofol)

What are the clinical consequences of the CSF favoring hydrophobic diffusion?

• hydrophilic drugs have very limited access

• bacterial infections are very rare

ISF vs. plasma

• ISF has:

  • lower PH (7.33) from elevated CO2 levels

    • 50 mmHg vs 45 mmHg in plasma

  • lower protein content

    • 0.2 g/L compared to 68-83 g/L in plasma

  • lower buffering capacity and less bicarbonate ions

  • lower glucose content

  • lower K+ content

What is the consequence of differences between ISF and plasma?

the CNS is very sensitive to changes in plasma CO2 levels

CNS pathologies related to BBB disruption

• traumatic brain injury

• hypertension

• diabetes

• ischemia, hypoxia

• migraines

• MS

• HIV-encephalitis

• cerebral malaria

• bacterial meningitis

• Covid-19

• epilepsy

• depression

• schizophrenia

• Alzheimer’s

• Parkinson’s

cerebral spinal fluid (CSF)

• located around and within the CNS

• source of solutes and water for ISF

functional roles of CSF

• buoyancy

  • brain without CSF weighs 1400 gm vs. <60 with CSF

• protection against trauma

• ISF functional stability

• removal of waste products

production of CSF

• via ependymal cells lining ventricles (fluid filled sacs)

ependymal cells

line ventricles and form choroid plexus with capillaries

CSF composition

• more like ISF than plasma

• 500 mL/day production

• 150 mL at one time

• mainly water (99%) with smaller percentages of

  • proteins

  • glucose

  • ions (Na+, K+, Cl-, and Ca2+)

How does sleep affect the flow of CSF?

• it triggers rhythmic waves of blood and CSF, which function like washing machine’s rinse cycle

• in a study with 13 young healthy people during sleep

  • fMRI analysis showed slow waves of electrical activity leading to alternating waves of blood and CSF

neuroglia

• over 50% of volume and supporting role, 90% of cells within the CNS

• internal environment

• communication

• guiding axons to right targets

• establishing synapses

• BBB

• removing debris

• producing CSF and myelin

• generating electrical currents

• taking up NT and ions

physiology of neuroglia cells

• surround

  • keep neurons in proper place

• support

  • nutrients and O2

• insulation

  • prevent axons from touching

• housekeeping

  • removal pathogens and dead cells

• development

  • axonal migration during fetal development

• synaptic transmission

  • NT removal, neuromodulators

oligodendrocytes

• CNS glia cell for myelin production about 1mm

• regulation of axonal growth

cerebral palsy

loss of CNS oligodendrocytes

astrocytes

• most abundant

• multiple types

• provide surface coverage, limiting solute movement into interstitial fluid

• part of the BBB

• regulation of CSF content

microglia

• specialized macrophages

• removal of debris, damaged cells, foreign substances

radial glia

scaffolding in which new neurons migrate