Cisterna magna injections are the most favorable administration route of cells and various agents to ensure their distribution to more rostral brain regions in mice and rats compared to intrathecal injections. Furthermore, injections of various tracer molecules into the cisterna magna are used to track the cerebrospinal fluid´s (CSF) movement through the glymphatic system in rodents. This recently discovered pathway is shown to be involved in the clearance of toxic metabolic solutes. It further increases the permeability of many agents through the blood-brain barrier compared to peripheral treatments; all speaking in favor for injecting compounds directly into the CSF.
To minimize the leakage of the injected substance through the dura mater we combined various known techniques resulting in only a minimal substance loss in rodents.
Figure 1. Schematic illustration of a cisterna magna injection in rodents using a Hamilton syringe. After injection, CSF sampling can be performed either repeatedly or terminally.
Prior to the injection, animals are anesthetized by isoflurane inhalation. Once anesthetized, the animal is placed in a stereotaxic apparatus and the incision site beneath the occipital bone is prepared by shaving and disinfecting the skin. The Hamilton syringe is placed in a specific angle to prevent damage to the blood vessels as well as to the spinal cord and thus to minimize loss and contamination of the CSF.
After proper healing of the injection side, CSF collection can be performed either repeatedly by in vivo collection or terminally during tissue collection. CSF is a valuable source of pharmacodynamic and prognostic biomarkers to reflect biochemical changes occurring during the development and progression of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington disease, amyotrophic lateral sclerosis, lysosomal storage diseases, and many more. CSF collections are performed with an up to 100% efficiency rate of collecting pure liquor without blood contamination. Cisterna magna injections might also be of relevance for gene therapy studies.
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