Intracerebroventricular injection
This route of administration is often used to bypass the blood-brain barrier because it can prevent important medications from reaching the central nervous system.
This injection method is widely used in diseased mice models to study the effect of drugs, plasmid DNA, and viral vectors on the central nervous system.
This protocol works by damaging the control level of cerebral glucose metabolism to mimic Alzheimer's disease symptoms.
[1] These ICV injections result in models for the sporadic Alzheimer's disease (sAD) form, rather than familial.
In the clinic, as well as independent experiments, an increase in amyloid beta (Aβ) levels in the brain has been seen to cause Alzheimer-like symptoms.
Examples of these studies include injection of bromodeoxyuridine for proliferation tracing, Apelin-13 for cerebral ischemia, and α-interferon for its antiviral and antibiotic properties.
It is assumed that the number of labeled nuclei after BrdU administration is an indicator of the intensity of cell proliferation.
In the study, there was an increase in BrdU-positive nuclei in the parenchyma for ICV injection compared to the levels for intraperitoneal administration.
This indicates a greater level of the tracer is introduced when injected directly into the ventricular cerebrospinal fluid.
However, severe central nervous system symptoms occur after injection for ICV, intravenous, and intramuscular routes of administration.
For some of these therapeutics, the administration of the drug directly into the central nervous system is optimal for the treatment of neurological disorders, while avoiding a severe immune response.
[7] In addition to these therapies, ICV injection has been used for the delivery of chemotherapies, treatment of carcinomatous meningitis, and other neurological disorders.
The results of this showed that AAV2/1 had higher expression in the cortical layers while penetrating less to the midbrain compared to the AAVDJ8 and AAV9 serotypes.
The results indicate that ICV injection of AAV vectors is successful for having a lasting expression of the transgene.
However, multimodal therapy using intra-CSF chemotherapy has shown promise in overt leukemic or lymphomatous meningeosis and primary CNS lymphomas.
This form of chemotherapy is less toxic while maintaining similar efficacy to cranial irradiation, by preventing the infiltration and proliferation of leukemic and tumor cells into the leptomeninges.
These seven patients were being treated for varying neurodegenerative disorders including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), progressive multiple sclerosis (MS-P), Parkinson's, spinal cord injury, traumatic brain injury, and stroke.
Six patients with either refractory trigeminal neuralgia or cluster headaches were treated with an ICV opiate infusion pump.
ICV pumps are typically kept in and replaced every four to five years, making the procedure ideal for patients with chronic pain.
This is due to the noradrenergic pain inhibitory system that is employed by these drugs, coupled with spinal receptors that produce analgesic effects.
The results of this study indicate that ICV injection of these drugs decreases thermal and mechanical hypersensitivity in a murine chronic pain model that has partial ligation of the sciatic nerve.
Also, intracranial pressure, cerebrospinal fluid bulk flow rate, and buffering capacity have an impact on the distribution and safety of the injected drug.
An ICV device is implanted under the scalp, into the subgaleal space where it is then connected to the ventricles with an outlet catheter.
Rarely will repeated taps be conducted to administer drugs due to the risk of damaging brain tissue.
