Restorative Neurology and Neuroscience

Purpose: Immunomodulatory agents are often combined in organ transplantation to minimize toxicity and enhance therapeutic effect. We hypothesized that combining low-dose FK506 with anti-CD40 Ligand (anti-CD40L mAb) would enhance regeneration through peripheral nerve allografts while preserving immune unresponsiveness.

Methods: Eighty Balb/cJ mice underwent tibial nerve grafting and were randomized to 10 groups treated with combinations of anti-CD40L mAb therapy, low-dose FK506 (0.5 mg/kg/day), high-dose FK506 (2 mg/kg/day), and high-dose cyclosporine (25 mg/kg/day). At 3 weeks, histomorphometry and cytokine secretion assays were performed.

Results: Animals receiving low-dose FK506 with anti-CD40L mAb exhibited robust nerve regeneration comparable to the isograft and high-dose FK506 allograft groups. Nerve density was significantly increased in the low-dose FK506 with anti-CD40L mAb group compared to animals receiving anti-CD40L mAb alone (p < 0.05). Combining anti-CD40L mAb with high dose cyclosporine decreased nerve fiber counts, nerve density, and percent nerve (p < 0.05). Interferon-γ production was markedly elevated in untreated allografts compared to all other treatment groups (p < 0.05). Cytokine secretion was intermediate in the low-dose FK506 alone group and suppressed in all remaining groups.

Conclusion: When combined with anti-CD40L mAb, low-dose FK506 enhances nerve regeneration without disrupting immune unresponsiveness.

Purpose: The purpose of this study was to examine the effects of dimerized basic fibroblast growth factor (dFGF), a novel engineered growth factor, in a model of functional recovery following focal cerebral infarction (stroke) in rats.

Methods: A focal stroke was made in mature male rats by occlusion of the middle cerebral artery (MCA). dFGF was administered by intracisternal injection at one and three days after stroke. Tests to evaluate sensorimotor recovery of the contralateral limbs were done during the next three weeks after stroke.

Results: dFGF significantly enhanced recovery of sensorimotor function in limb placing and body swing tests compared to vehicle treatment. There were no differences in body weight or infarct volume in dFGF- vs. vehicle-treated animals.

Conclusions: dFGF represents a potential treatment to enhance functional recovery after stroke and offers several advantages over bFGF, including stability and independence from extracellular heparan sulfates.

Purpose: Previous studies investigating relationships between stroke lesion volume and outcome were restricted to short follow-up periods (3–6 months) and outcome measures of stroke severity and activities only, whereas functional improvement has been found to extend far beyond six months. Therefore, this study investigated relationships between infarct volume and a broad range of outcomes of stroke survivors at a long follow-up period.

Methods: Correlations between lesion volumes (determined by conventional MRI scans in the second week post-stroke) and outcomes after one year of 75 first-ever ischemic stroke survivors were investigated.

Results: Moderate Spearman Rank correlation coefficients were found between lesion volume and motor impairment (Motricity Index (MI): −0.43, p < 0.01; Fugl Meyer Motor Assessment Scale (FM): −0.43; p < 0.01). Correlation coefficients with activities of daily living were moderate but low associated with Barthel Index (r $_s$ = 0.30; p < 0.01), modified Rankin Scale (r $_s$ = 0.39; p < 0.01) and Frenchay Activities Index (r $_s$ = −0.35; p < 0.01). Lesion volume had a significant but low association (r $_s$ = 0.27; p = 0.02) with patient's health status measured with Sickness Impact Profile 68 (SIP68)) and a moderate correlation with well-being assessed with Life Satisfaction Questionnaire (LSQ; r $_s$ = −0.45; p < 0.01). Found correlation coefficients were slightly stronger after correction for mixed (cortical/subcortical) and purely subcortical lesion location.

Conclusions: It can be concluded that infarct volume moderately correlates with long-term motor impairment, functional outcome and quality of life of patients surviving stroke.