Tongxinluo is associated with neurovascular changes following rt-PA-treated ischemic stroke: associations with inflammation, vascular remodeling, and neural plasticity
Year: 2026
Type: article
Abstract: Background: Recombinant tissue plasminogen activator (rt-PA) is the standard treatment for acute ischemic stroke but is often limited by microvascular obstruction and reperfusion injury. Tongxinluo (TXL) has demonstrated neuroprotective potential, yet its association with neurovascular responses during rt-PA-associated reperfusion remains incompletely characterized. Methods: Because reperfusion was achieved by filament withdrawal before rt-PA administration, this model evaluates TXL-associated effects during mechanically induced reperfusion with rt-PA exposure rather than enhancement of rt-PA-mediated thrombolysis. Animals were randomized into Sham, MCAO, MCAO + rt-PA, and MCAO + rt-PA + TXL (low/high dose) groups. Neurological outcomes were assessed longitudinally. Cerebral perfusion was monitored using laser speckle contrast imaging (LSCI). Mechanistic analyses included assessments of blood-brain barrier (BBB) integrity, oxidative stress, microglial activation, angiogenesis, mitochondrial function, apoptosis, and synaptic plasticity markers (BDNF, GAP-43, and Synapsin I) using histological, biochemical, and molecular techniques. Results: Adjunctive TXL treatment was associated with improved neurological outcomes and reduced infarct volume compared with rt-PA alone, with dose-dependent trends observed. TXL was associated with improved cortical microvascular perfusion and reduced severity of the no-reflow phenomenon. Mechanistically, TXL suppressed microglia-mediated neuroinflammation (downregulating TNF-α, IL-1β, and IL-6) and preserved BBB integrity. This anti-inflammatory environment facilitated angiogenic maturation, evidenced by increased microvessel density and lumen formation. Furthermore, TXL stabilized mitochondrial function, inhibited neuronal apoptosis, and upregulated BDNF, GAP-43, and Synapsin I, leading to significant restoration of dendritic spine density. Conclusion: TXL may provide adjunctive neuroprotective effects in the context of rt-PA treatment by modulating inflammatory, vascular-associated, and neuronal recovery responses. These findings support further investigation of TXL as a complementary therapy following reperfusion. By concurrently suppressing neuroinflammation and promoting vascular and synaptic reconstruction, TXL translates multi-target modulation into robust functional recovery, supporting its potential as a strategic combination therapy for acute ischemic stroke.
Source: Frontiers in Neurology
Authors: Meiling Xiao, Wei Ding, Xiaoqu Zuo, Hongwu Tao
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7221764940