Perineuronal nets (PNNs) are extracellular molecules that form around neurons near the end of critical periods during development. They surround neuronal cell bodies and proximal dendrites. PNNs inhibit the formation of new connections and may concentrate around rapidly firing inhibitory interneurons. Previous work characterized the important role of perineuronal nets in plasticity in the visual system, amygdala, and spinal cord of rats. In this study, we use immunohistochemistry to survey the distribution of perineuronal nets in representative areas of the primate brain. We also document changes in PNN prevalence in these areas in animals of different ages. We found that PNNs are most prevalent in the cerebellar nuclei, surrounding >90% of the neurons there. They are much less prevalent in cerebral cortex, surrounding less than 10% of neurons in every area that we examined. The incidence of perineuronal nets around parvalbumin-positive neurons (putative fast-spiking interneurons) varies considerably between different areas in the brain. Our survey indicates that the presence of PNNs may not have a simple relationship with neural plasticity and may serve multiple functions in the central nervous system.

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Introduction: Age is a major risk factor for Cerebral Small Vessel Disease (CSVD) and poor functional outcome following acute ischemic stroke (AIS). Recently, white matter hyperintensity (WMH), a surrogate for CSVD has been associated with AIS poor functional outcome. We aimed to investigate the effect of the total MRI load of CSVD features on AIS functional outcome and their relationship to age. Methods: Patients presenting with AIS were prospectively recruited. Baseline characteristics, in-hospital complications, acute therapies and discharge dispositions were collected. Total CSVD disease burden (WMH, lacunes, microbleed (MB) and enlarged perivascular space (PVS)) was measured on the first MRI within 24 hour of hospital admission using (0-4) scale according to Staals et al, Neurology 2014. Univariate analysis was completed using t-test, Mann-Whitney Rank Sum test, Chi square test or Spearman correlation as appropriate. Multivariate logistic regression analysis was performed to adjust for the effect of age, stroke volume and CSVD score on the functional outcome of AIS. Results: 99 subjects with AIS were analyzed (age 65.4±13.7, 52.5% females). 68.4% of patients had favorable discharge outcome (home or acute rehabilitation). CSVD features were present in the cohort as the following: 41.2% had lacunes, 26.4% had MBs, 70.1% had more than 10 PVS in the basal ganglia and 42.4% had Fazekas score of periventricular WMH of 3 or deep WMH of 2 or above. Total CSVD score was 1.6±1.4, and correlated with age (p=0.0015) but not with stroke volume (p=0.71). Unfavorable stroke outcome was associated with higher stroke volume, CSVD score and age (p =0.0005, 0.003 and 0.012, respectively). This relationship remained significant in multivariate analysis for CSVD (p=0.008) and stroke volume (p=0.004) but not for age (p=0.72). Conclusions: CSVD burden on MRI is associated with worse functional outcome of AIS. This effect appears to be independent of the effect of age on AIS outcome. These results need to be validated in larger cohorts.