Worst spasticity in patients post-stroke associated with MNSOD ALA16VAL polymorphism and interleukin-1ß.

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of several metabolic and vascular diseases. However, little is known about interaction between MnSOD Ala16Val SNP in stroke, a frequent neurologic disease that involves clinic manifestations such as motor deficits and spasticity. In this sense, we decided to investigate the relationship between MnSOD Ala16Val SNP with spasticity in stroke and also its influence on interleukin levels, BDNF, and glycolipid parameters. Eighty post-stroke subjects and 80 healthy controls were investigated. We showed a higher spasticity, levels of total cholesterol, LDL, IL-1ß, IL-6, and INF-γ in VV post-stroke group. Interesting, we found a correlation between IL-1ß levels and spasticity in VV post-stroke. Triglycerides, glucose levels and caspases (1 and 3) activation were significantly higher, as well as BDNF levels were lower in VV and AV post-stroke. DNA damage was higher in post-stroke group. Thus, we can suggest that the V allele has a worse glycolipid profile, which would facilitate changes in neurovascular homeostasis. These events associated with an increase in inflammatory markers and a reduction in BDNF can contribute with the stroke and a worse clinical evolution in relation to spasticity in patients with VV genotype.

Apoptotic Markers Are Increased in Epilepsy Patients: A Relation with Manganese Superoxide Dismutase Ala16Val Polymorphism and Seizure Type through IL-1ß and IL-6 Pathways.

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has been associated with different diseases. However, there are scarcely studies relating this SNP in epilepsy, a neurologic disease that involves some interacting pathways, such as apoptotic and inflammatory factors. In this sense, we decided to investigate the relationship of MnSOD Ala16Val SNP with apoptotic markers in epilepsy and its relation with inflammatory pathway and seizure type. Ninety subjects were evaluated (47 epilepsies; 43 controls) by questionnaires and laboratorial exams. We observed a higher percentage of VV genotype in the epilepsy group when compared to the control group. IL-1ß, IL-6, caspase-1, and caspase-3 levels were increased in the epilepsy group (VV genotype). Furthermore, an important correlation between IL-1ß vs. caspase-1 and IL-6 vs. caspase-3 was observed in the epilepsy group (VV genotype). The epilepsy group which presented generalized seizures also demonstrated a positive correlation between IL-1ß vs. CASP1 and IL-6 vs. CASP3. Thus, it is a plausible propose that epilepsy patients with VV genotype and generalized seizures present a worse inflammatory and apoptotic status. Our findings suggest that the knowledge of MnSOD Ala16Val polymorphism existence is important to evaluate molecular mechanisms associated to seizure and improve the treatment of these patients.

Involvement of MnSOD Ala16Val polymorphism in epilepsy: A relationship with seizure type, inflammation, and metabolic syndrome.

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to inflammatory pathways and many metabolic disorders, such as obesity and dyslipidemia. Metabolic syndrome (MetS) is an emergent problem among patients with epilepsy. However, little is known about interaction between MnSOD Ala16Val SNP and metabolic comorbities in epilepsy. Thus, we investigated the relationship between MnSOD Ala16Val SNP with epilepsy and its influence on MetS, inflammation, apoptosis and DNA damage parameters. Ninety subjects were evaluated (47 epilepsy patients and 43 healthy controls) by questionnaires and laboratorial exams. Levels of inflammatory, apoptotic and DNA damage markers, as well as MnSOD polymorphism were assessed. An increased proportion of VV genotype in epilepsy group when compared to control group was observed. Tumor Necrosis Factor-α (TNF-α), Acetylcholinesterase, caspase-8, and Picogreen levels were increased in VV epilepsy group. An important correlation between TNF-α vs caspase-8, and Cholesterol vs. Triglycerides was observed in the epilepsy group with VV genotype. Our findings suggest that the MnSOD Ala16Val SNP might have an important role in epilepsy, mainly in patients with generalized seizures and particularly with VV genotype. The metabolic parameters also presented significant results in epilepsy group with VV genotype, which applying attention in view of further consequences and disorders that could be developed.

ALA16VAL-MnSOD gene polymorphism and stroke: Association with dyslipidemia and glucose levels.

Stroke risk has been associated to the progression of carotid plaques due to high glucose levels and lipid accumulation, which are greatly associated to cerebral injury, brain oxidative stress, and apoptosis. The ALA16VAL-MnSOD gene single nucleotide polymorphism (SNP) has shown to modulate risk factors of several metabolic and vascular diseases, such as blood glucose (GLU) and lipid levels. However, the association of these factors in stroke patients has not been studied to date. Thus, we evaluated the influence of the Ala16Val-MnSOD SNP on lipid profile, GLU levels, oxidative and DNA damage of 44 patients in a late phase of stroke (>6months). The statistical analysis showed a greater proportion of VV carries in stroke patients. The results also indicated that stroke patients had higher cholesterol (CHO) and GLU levels when compared to healthy counterparts. Interestingly, V allele carriers with stroke showed higher levels of CHO and GLU when compared to AA stroke and healthy counterparts. Our findings suggest that oxidative stress markers are still increased even after 6 months of cerebral injury. Furthermore, we propose that the Ala16Val-MnSOD SNPs may contribute to hypercholesterolemia and higher GLU levels, increasing the risk to neurovascular events that may lead to stroke.

Apoptotic markers and DNA damage are related to late phase of stroke: Involvement of dyslipidemia and inflammation.

Oxidative stress and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke, leading to apoptosis and cell death. Lipid accumulation may lead to progression of carotid plaques and inflammation, contributing to increased acute stroke risk. However, little is known about these events and markers in the late stroke (>6 months) and if dyslipidemia could contribute to disease's pathophysiology in a later phase. In this case-control study, we recruited patients in the late stroke phase (n=40) and health subjects (control group; n = 40). Dichlorodihydrofluorescein (DCFH), nitrite/nitrate (NOx), Tumor necrosis factor-alpha (TNF-α), Acetylcholinesterase (AChE), Caspase 8 (CASP 8), Caspase 3 (CASP 3) and Picogreen (PG) were measured in periphery blood samples. Furthermore, a correlation among all measured markers (DCFH, NOx, TNF-α, AChE, CASP 8, CASP 3 and PG) was realized. The marker levels were also compared to triglycerides (TG), total (CHO), LDL and HDL cholesterol levels and medications used. Statistical analyses showed that stroke patients presented an increase of DCFH, NOx, TNF-α and AChE levels when compared to control subjects. In addition, we observed that stroke patients had significantly higher CASP 8, CASP 3 and PG levels than control group. A significant correlation between TNF-α with CASP 8 (r = 0.4) and CASP 3 (r = 0.4) levels was observed, but not with oxidative/nitrosative markers. Moreover, we observed that stroke patients with dyslipidemia had significantly higher TNF-α, CASP 8 and CASP 3 levels than stroke without dyslipidemia and control groups. Our findings suggest that oxidative and inflammatory markers may be still increased and lead to caspase activation and DNA damage even after 6 months to cerebral injury. Furthermore, it is plausible to propose that dyslipidemia may contribute to worsen proinflammatory state in a later phase of stroke and an increased risk to new neurovascular events.