Biomedical Engineering Reference
In-Depth Information
Neurodegenerative diseases greatly benefi t from therapeutics that
can enter directly into the CNS. In humans, this type of delivery is
through surgical procedures of intrathecal injection (lumbar punc-
ture) and intraventricular injection. Intrathecal delivery is common
in chemotherapy treating leukemia found in the brain and spinal
cord and also stem cell therapy for spinal cord injuries [
95
].
Intraventricular injection in humans is conducted by delivering the
therapeutic agent into a specialized catheter called an Ommaya res-
ervoir that is placed into the lateral (outer) ventricle of the brain.
This procedure is used most commonly in acute leukemia but can
be used in other situations as well. In preclinical studies using mice,
CNS delivery can be achieved by injecting directly into the cerebral
lateral ventricles (intracerebroventricular) at neonatal stages. This
type of injection will result in the delivery of materials into the CNS
through the cerebrospinal fl uid. The primary benefi t is direct deliv-
ery into the CNS and effectively bypassing the blood-brain barrier.
Therefore, this type of injection will allow the analysis of the viral
vector or any other compound that is not fully optimized for drug-
like properties (such as blood-brain barrier permeability) for their
effectiveness in disease-relevant tissues. Extensive transduction of
the CNS by ICV injection is feasible depending on the appropriate
choice of viral vector, serotype, viral titer, and more importantly the
time of the application. The ICV injections performed by freehand
require the skull to be relatively pliable. Therefore, this type of
injection is only possible through the fi rst week of life. As the ani-
mals age, the hardening of the skull makes this procedure increas-
ingly diffi cult and harmful to the animals [
96
].
2
Materials
See
Table
1
.
Table 1
Materials and tools required for ICV injection into the mouse brain
Materials/tools
Company
Cat. #
Food dye
McCormic
N/A
Kimble
TM
disposable micro
capillary pipettes
Fisher Scientifi c 13-678-18A
P-97 Flaming/Brown
micropipette puller
Sutter Instrument N/A
Plastic syringe
BD Biosciences
305269
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