It is well-known that hyaluronic acid (HA) as a component of brain extracellular matrix (ECM) plays a pivotal role in the nervous system and is involved in synaptic plasticity changes in vascular cognitive impairment and dementia. HA breakdown is a feature of the acute stage of stroke injury and may be detrimental through enhancement of the inflammatory response. Recent studies have shown that knockout mice lacking hyaluronic acid synthetase demonstrates epileptic phenotype in vivo and removal of HA leads to delayed development of epileptiform activity in cultured hippocampal neurons in vitro. Here, we studied whether digestion of hyaluronic acid in the hippocampus in early postnatal period can trigger seizures. Hyaluronidase (Hyal) (5 U/μl) was bilaterally injected into C57BL/6j mice (P17) CA1 field of hippocampus using the stereotaxic method to remove hyaluronan-based ECM. Transcriptome analysis of hippocampal tissue 2 h after enzymatic digestion of hyaluronan-based brain ECM revealed increased gene expression of proteins involved in inflammation reactions (TLR2, CCL2,3,5), neuroinflammation, axonal guidance and ephrin receptor signaling, versus the vehicle group. Mice injected with hyaluronidase exhibited delayed audiogenic seizures and improvement in working memory 72 h after injection, while there were no changes in locomotor activity, anxious level and exploratory behavior due to the open field test. The obtained results point to a link between the activation of neuroinflammation by enzymatic digestion of hyaluronan-based brain ECM during the neonatal period and their subsequent reactivity to seizures, which may play an important role in the functional features of the developing brain, including its seizure propensity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.