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Printable Handouts
Navigable Slide Index
- Introduction
- Talk outline
- Part 1
- The blood-brain barrier (BBB)
- The BBB is an immense regulatory interface
- The BBB controls nutrient influx & toxin efflux
- "Peptides do not cross the BBB": a misconception
- Heterogeneity of the brain barriers
- Interstitial space, CSF & cellular compartments
- Most important aspect of the neurovascular unit
- Methods to tackle the BBB
- BBB permeability & cytokine transport regulation
- Differential permeability of the BBB
- Obesity & metabolic disorders
- Cytokine transport and signaling
- Part 2
- Neurotrophic protein transport across the BBB
- NGF 30 minutes after iv injection
- Capillary depletion 10 minutes after iv
- New technologies to study brain barrier dynamics
- Other neurotrophic proteins & peptides
- A few representative proteins
- BBB targeting of BDNF
- BDNF 60 min after iv
- BDNF entering brain parenchyma
- How does BDNF reach the brain?
- Efflux transport affects BDNF fate
- LIF (Leukemia inhibitory factor)
- LIF mainly shows reversible vascular binding
- Spinal cord has similar saturable kinetics to brain
- Influx saturation in blood-free in-situ perfusion
- Growth hormone: lack of saturable transport
- GH: significant uptake by brain parenchyma
- EGF: a neurotrophic peptide
- Degradation of EGF
- Radioactivity denotes EGF entering parenchyma
- TGFα shares transport system with EGF
- Blocking EGFR doesn't reduce EGF influx
- Mice without functional EGFR maintain transport
- There is no efflux transport system for EGF
- Part 3
- Enhancing CNS delivery of peptides & proteins
- IGF-I bypasses BBB & protects against damage
- Neuroprotective bFGF effects in brain ischemia
- BDNF gene delivery to CNS with bone marrow cells
- Model of MPTP-induced Parkinson’s disease
- Limitations & progress
- Strategies to improve neuro-regeneration
- Part 4
- BBB regulatory roles in wakefulness & sleep
- Chronic sleep restriction impairs BBB function
- Effects of sleep & circadian rhythm on BBB
- The BBB as a source of CSF
- Summary
Topics Covered
- Overview of neurotrophins
- CNS physiology and roles in neuroregeneration
- The blood-brain barrier (BBB)
- General strategies to enhance CNS delivery
- Progress on neurotrophin delivery across the BBB
- Limitations and future directions
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Pan, W. (2017, January 31). Transport and delivery of neurotrophic peptides and proteins across the BBB [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 7, 2024, from https://doi.org/10.69645/AVUG1968.Export Citation (RIS)
Publication History
Financial Disclosures
- Professor Weihong Pan has no commercial/financial relationships to disclose
A selection of talks on Neurology
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, I am Dr. Weihong Pan.
In this slide set,
I will discuss "Transport
and Delivery of Neurotrophic Peptides
and Proteins across the BBB".
0:12
Here is the outline.
The first part is about
the blood-brain barrier,
or BBB in short,
to peptides and proteins
with a discussion of flow-independent
influx transport systems.
The second part addresses
influx transport
of neurotrophic peptides and proteins.
The third part
will move to the biotechnology sector
and the goals of CNS drug delivery.
The last part
will focus on physiological regulations,
particularly those related to sleep
and the circadian rhythms.
0:47
In part one,
I will have a brief review
of pertinent features of the BBB,
discuss the dynamic context
involving interstitial space,
cerebrospinal fluid or CSF,
and the cellular compartments.
I will then summarize study methods
including the classics and updates.
1:10
To formulate the image
of a three-dimensional
blood-brain barrier,
let's first take a sample
of 1 square millimeter of brain tissue.
If it is from an
adult human cerebral cortex,
within the 1 square millimeter,
there will be about 50,000 neurons
and 300 million synapses.
No neuron is more than 8 microns away
from a microvessel,
as well as glial cells.
The density of microvessels
is clearly seen
from the vascular corrosion cast image,
in the upper right circle.
Each artery branches to arterioles,
then capillary beds
that has a vast surface area,
and finally,
they drain into venules and small veins.
In the capillaries and the venules
where blood flow is very slow
and conducive to exchange
of fluid components,
that's where the BBB
shows a unique structure
that varies among species.
In general, the microvessel wall
lacks fenestration
and is reinforced by tight junctions
and adherent junction complexes.
This greatly reduces
vascular permeability
and makes specific transport systems
extremely important.
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