PB0838 - Neuroprotective effects of a Low-anticoagulant Bovine Heparin on Intracerebral Hemorrhage Model in Rats.

Background: The expansion of hematoma following intracerebral hemorrhage (ICH) is associated with deteriorating neurological conditions and poor outcomes. Primary risk factors for ICH include hypertension and the use of specific antithrombotics. Paradoxically, heparin has demonstrated anti-inflammatory and neuroprotective effects in both preclinical and clinical studies. However, its application is limited by potential adverse bleeding effects.

Aims: This study employed various neuromotor tests to characterize the temporal neurological decline associated with ICH and investigated the neuroprotective potential of a low anticoagulant bovine heparin (LABH) using healthy Wistar and spontaneously hypertensive rats (SHR). Warfarin served as a positive control for ICH expansion associated with anticoagulant therapy.

Methods: LABH at 4 mg/kg was intravenously administered 5 minutes prior to collagenase injection into the left brain striatum to induce ICH, followed by subcutaneous administrations at 10 or 20 mg/kg over the subsequent 3 days. Neurological tests (Garcia Scale, Rotarod, and Catwalk analysis) were conducted over time. Hematomal lesion volume was determined via Evans Blue extravasation. Statistical analysis utilized OriginPro 2018 software, with significance assessed through one-way analysis of variance and Bonferroni’s post-hoc test. We followed the institutional guidelines for animal care and experimentation (approval protocol number 019/23).

Results: Animals treated with warfarin exhibited an increase in Evans Blue extravasation, while SHR demonstrated values similar to healthy animals subjected to the ICH model. Wistar rats exhibited a poor neurological score in the initial week, recovering approximately 10 days post-hemorrhagic insult. Conversely, SHR displayed a worse neurological score than healthy animals in the ICH model, particularly in the first week. LABH treatment, notably at 10 mg/kg, prevented neurological decline associated with ICH at days 2 and 4 (Table 1), as demonstrated by improvements in neurological score and Rotarod performance.

Conclusion(s): LABH shows promise as a compound for further studies aimed at validating its neuroprotective effects in both normal and SHR rats.