[Show abstract][Hide abstract] ABSTRACT: Thyroid hormones (TH) and receptors (TRs) may play an important role in the pathophysiology of acute cerebral ischemia. In the present study, we sought to determine whether serum triodothyronine (T3)/thyroxine (T4) and brain TRs (TRα1, TRβ1) might change after experimental stroke. Male adult Wistar rats were subjected to permanent middle cerebral artery occlusion (group P) and compared to sham-operated controls (group S). Animals were followed clinically for 14 days until brain collection for Western blot (WB) or neuropathological analysis of TRs in three different brain areas (infarcted tissue, E1; noninfarcted ipsilateral hemisphere, E2; and contralateral hemisphere, E3). Analysis of serum TH levels showed a reduction of T4 in group P (p = 0.002) at days 2 to 14, while half of the animals also displayed "low T3" values (p = 0.012) on day 14. This T4 reduction was inversely correlated to the clinical severity of stroke and the concomitant body weight loss (p < 0.005). WB analysis of TRα1 and TRβ1 protein expression showed heterogenic responses at day 14: total and nuclear TRα1 were similar between the two groups, while total TRβ1 decreased 7.5-fold within E1 (p ≤ 0.001) with a concomitant 1.8-fold increase of nuclear TRβ1 in E2 area (p = 0.03); TRβ1 expression did not differ in E3. Neuropathological analysis revealed that activated macrophages/microglia exclusively expressed nuclear TRα1 within the infarct core. Astrocytes mildly expressed nuclear TRα1 in and around the infarct, along with a prominent TRβ nuclear signal restricted in the astrocytic scar. Neurons around the infarct expressed mainly TRα1 and, to a milder degree, TRβ. Surprisingly enough, we detected for the first time a TRβ expression in the paranodal region of Ranvier nodes, of unknown significance so far. Our data support that cerebral ischemia induces a low TH response, associated with significant and heterogenic changes in brain TR expression. These findings could imply an important role of TH signaling in cerebral ischemia.
Journal of Molecular Neuroscience 02/2014; · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Intracerebroventricular (ICV) experimental route is highly promising due to immediate approach of a "therapy" to the cerebrospinal compartment. Ischemic edema causes structural dislocations and stereotaxia alterations after temporary Middle Cerebral Artery Occlusion (t-MCAO), while there is no similar study for intracerebroventricular (ICV) invasion after permanent MCAO (p-MCAO). Methods: Male Wistar rats were subjected to right p-MCAO and clinically evaluated 6 and 18 hours post-occlusion, using the modified Neurological Stroke Scale (mNSS) and modified Bederson's Scale (mBS). Infarction volume, hemispheric edema, middle line dislocation and stereotaxia of the lateral ventricles were studied at the same time-points. Results: P-MCAO induced mild but significant changes in the stereotaxia of the infarcted (ipsilateral) lateral ventricle on 18- (P<0.05), though not 6-hours (P>0.05) post-occlusion. These changes correlated with the mNSS and mBS scores (P<0.01) and allowed the expression of linear mathematical equations (stereotaxic coordinate = b0 + b1*mNSS; calculated by regression analysis) predicting the new ventricular position in each individual animal. The contralateral ventricular system was structurally unaffected on both time-points. Verification experiments indicated that the new coordinates were necessary on 18-hours post-occlusion for successful ICV invasion in all p-MCAO rats (Number Needed to Treat 2.28), compared to 56.25% success when using the classical coordinates for normal rats. Conclusion: P-MCAO causes relatively late but predictable stereotaxia shifts for ICV invasion, which are different compared to t-MCAO.
[Show abstract][Hide abstract] ABSTRACT: Alzheimer disease (AD) is a progressive, fatal neurodegenerative condition.
We tested the hypothesis that eradication of Helicobacter pylori infection (Hp-I) could improve survival in a Greek cohort of AD patients, in a 5-year follow-up.
Forty-six patients diagnosed with probable AD were enrolled in the analysis. Study population was classified into 3 groups: patients for whom Hp eradication treatment was successful; those for whom eradication of Hp had failed, they refused, and/or were noncompliant with eradication therapy; and those who were Hp negative at baseline. Cox proportional hazards model was built with all-cause mortality as the dichotomous outcome.
During the 5-year follow-up [47.19±15.11 mo (range 12 to 60)], overall 21 patients died and 25 patients remained alive. Patients who died were older and exhibited lower mean MMSE score compared with the patients still alive. Successful eradication of Hp-I was associated with a significantly lower mortality risk [HR (95% CI)=0.287 (0.114-0.725), P=0.008]. The results were similar in adjusted and unadjusted models, for age and MMSE at baseline.
Hp eradication regimen in AD patients is associated with a higher 5-year survival rate.
Cognitive and behavioral neurology: official journal of the Society for Behavioral and Cognitive Neurology 09/2010; 23(3):199-204. · 1.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The human central nervous system (CNS) is targeted by different pathogens which, apart from pathogens' intranasal inoculation or trafficking into the brain through infected blood cells, may use a distinct pathway to bypass the blood-brain barrier by using the gastrointestinal tract (GIT) retrograde axonal transport through sensory or motor fibres. The recent findings regarding the enteric nervous system (often called the "little brain") similarities with CNS and GIT axonal transport of infections resulting in CNS neuroinflammation are mainly reviewed in this article. We herein propose that the GIT is the vulnerable area through which pathogens (such as Helicobacter pylori) may influence the brain and induce multiple sclerosis pathologies, mainly via the fast axonal transport by the afferent neurones connecting the GIT to brain.
Medical Hypotheses 06/2009; 73(5):781-7. · 1.18 Impact Factor