Treatment with albumin-hydroxyoleic acid complex restores sensorimotor function in rats with spinal cord injury: Efficacy and gene expression regulation

Abstract

Sensorimotor dysfunction following incomplete spinal cord injury (SCI) is often characterized by paralysis, spasticity and pain. Previously, we showed that intrathecal (i.t.) administration of the albumin-oleic acid (A-OA) complex in rats with SCI produced partial improvement of these symptoms and that oral 2-hydroxyoleic acid (HOA, a non-hydrolyzable OA analogue), was efficacious in the modulation and treatment of nociception and pain-related anxiety, respectively. Here we observed that intrathecal treatment with the complex albumin-HOA (A-HOA) every 3 days following T9 spinal contusion injury improved locomotor function assessed with the Rotarod and inhibited TA noxious reflex activity in Wistar rats. To investigate the mechanism of action of A-HOA, microarray analysis was carried out in the spinal cord lesion area. Representative genes involved in pain and neuroregeneration were selected to validate the changes observed in the microarray analysis by quantitative real-time RT-PCR. Comparison of the expression between healthy rats, SCI rats, and SCI treated with A-HOA rats revealed relevant changes in the expression of genes associated with neuronal morphogenesis and growth, neuronal survival, pain and inflammation. Thus, treatment with A-HOA not only induced a significant overexpression of growth and differentiation factor 10 (GDF10), tenascin C (TNC), aspirin (ASPN) and sushi-repeat-containing X-linked 2 (SRPX2), but also a significant reduction in the expression of prostaglandin E synthase (PTGES) and phospholipases A1 and A2 (PLA1/2). Currently, SCI has very important unmet clinical needs. A-HOA downregulated genes involved with inflammation and upregulated genes involved in neuronal growth, and may serve to promote recovery of function after experimental SCI.

A spinal cord injury time and severity consensus transcriptomic reference suite in rat reveals translationally-relevant biomarker genes

“…After full-text evaluation, we excluded six more studies due to the lack of control samples without treatment or information. Finally, we included 14 studies in our meta-analysis (table S1) (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Synapses, Microglia, and Lipids in Alzheimer’s Disease

“…They also reported that SRPX2 (–/Y) knockout mice have increased C3 deposition and microglial synapse engulfment in the dorsal lateral geniculate nucleus (dLGN). Avila-Martin et al (2017) further reported that albumin-hydroxyoleic acid complex (A-HOA) promoted sensorimotor function recovery in rats with spinal cord injury (SCI) by upregulating several genes including SRPX2, suggesting that SRPX2 may play a role in reestablishing vascularisation and recovering synapse loss associated with SCI. In another study, Cong et al (2021) showed that the deletion of C1q resulted in a persistent decrease in microglia-mediated synapse elimination and engulfment in the visual cortex.…”

The combination treatment of methylprednisolone and growth factor-rich serum ameliorates the structural and functional changes after spinal cord injury in rat

“…On the day before SCI induction, the rats were tested by accelerating the speed from 5 to 20 rpm over 5 min. Then, 28 days after SCI, motor performance was examined with the same test conditions [21,22].…”