Stereotaxic surgery

Sylics offers a range of services related to stereotaxic surgeries directly into the central nervous system with a wide range of compounds.

Viral vectors

Expression of biological drugs in the central nervous system is becoming an increasingly attractive route of administration. These studies usually use adeno-associated virus (AAV) or lentivirus (LV) vectors, which upon administration induce expression of the RNA and/or protein of interest. Sylics has performed several studies in which, for example, disease-related genes have been expressed in the brain (Loos et al., 2014). Please contact us for more information.

Single ICV infusion

For testing certain compounds in preclinical studies (e.g. antisense oligonucleotides), it is required to infuse them into the cerebrospinal fluid (CSF) by Intracerebroventricular (ICV) injection. AAV vectors are often delivered ICV to induce widespread expression in the brain. Sylics has experience with infusing compounds in neonatal, young, and adult mice. Please contact us for more information.

Proteins

Disease related proteins (e.g. aggregates) or therapeutic proteins/peptides (e.g. monoclonal antibodies) are often injected into the central nervous system. This route of administration bypasses the blood brain barrier and allows targeting of specific brain regions. Localized injection leads to seeded aggregation and spreading for certain proteins, such as tau, alpha-synuclein, or TDP-43. Sylics has performed studies where in vitro formed protein aggregates were injected into the brain. Please contact us for more information.

Misfolded and aggregated α-synuclein accumulates into intraneuronal inclusions named Lewy bodies, shown as small red spheres inside neurons which are associated wuth progressive degeneration.
Progression of tau pathology in the weeks after infusion of human tau seeds into the hippocampus of htau mice, as detected by AT8 fluorescent staining.

Human brain extracts

Brain extracts from patients with neurodegenerative disorders are frequently injected into the brain of mice, to mimic the disease specific protein aggregation process. The most frequently used aggregates from the human brain include tau, alpha-synuclein, or TDP-43. Sylics has performed studies where brain-derived protein aggregates were injected into the brain of wild-type and transgenic mice. Please contact us for more information.

Localized lesions

Stereotaxic injection can be used to infuse neurotoxic compounds into the central nervous system. The most well known example is Oxidopamine (6-OHDA), which leads to selective loss of dopamine-producing neurons in the substantia nigra to model Parkinson’s disease. Another example is the administration of lysolecithin, which leads to acute toxicity to the myelin - thereby mimicking aspects of multiple sclerosis. Please contact us for more information.

Tyrosine hydroxylase staining can be used to assess dopaminergic cell loss after localized lesions in the substantia nigra.

Loos et al (2014) Biol Psychiatry

Neuregulin-3 in the mouse medial prefrontal cortex regulates impulsive action. Loos M, Mueller T, Gouwenberg Y, Wijnands R, van der Loo RJ; Neuro-BSIK Mouse Phenomics Consortium, Birchmeier C, Smit AB, Spijker S. Biol Psychiatry. 2014 Oct 15;76(8):648-55. doi: 10.1016/j.biopsych.2014.02.011. Epub 2014 Feb 24. PMID: 24703509. https://pubmed.ncbi.nlm.nih.gov/24703509/

More information

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