Therapeutic Potential of 2-(2-Benzofuranyl)-2-Imidazoline in Preclinical CNS Models: A Systematic Review of Mechanisms, Disease Models, and Cellular Targets
Abstract
Background/Objectives: 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) is a selective imidazoline I2-site ligand that has shown neuroprotective and neuromodulatory effects in preclinical central nervous system (CNS) studies. However, the primary preclinical literature remains fragmented across disease models, outcome types, mechanistic endpoints, and cellular targets, making it difficult to define where its therapeutic-development potential is strongest and how disease- or model-specific functional effects relate to molecular, cellular, tissue, and blood–brain barrier/neurovascular unit (BBB/NVU)-related findings. Methods: This systematic review integrated preclinical evidence from 36 original studies identified in the PubMed, Web of Science, Embase, and Scopus databases through searches last updated on May 19, 2026, to evaluate the strength of evidence for 2-BFI across CNS-related models and to connect functional, molecular, cellular, and neurovascular findings. The evidence categories included ischemic stroke/neurovascular outcomes (n = 13), traumatic CNS injury (n = 2), neuroinflammatory/neurodegeneration-related models (n = 9), behavioral pharmacology (n = 8), and cellular mechanisms (n = 4). Eligible studies were original CNS-related animal, cellular, or behavioral/pharmacological studies that directly evaluated 2-BFI and reported neuroprotective, neurological, cellular, molecular, vascular, inflammatory, neurotransmitter-related, or behavioral outcomes. Findings were…
How strong is the evidence?
Evidence Hub reads this as a systematic review. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 13 participants or records.
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