Correlation between left atrial expansion index and stroke subtype: A 10-Year Follow-Up Study.

PURPOSE: Although left atrial (LA) expansion index predicts cardiovascular events, its efficacy for predicting cerebral events is unknown. METHODS: This study enrolled 2205 patients who had sinus rhythm after echocardiography in their first visit. LA expansion index was calculated as (Volmax -Volmin ) x100%/Volmin , where Volmax was defined as maximal LA volume and Volmin as minimal LA volume. The study endpoint was ischemic stroke. Stroke subtype was classified as cardioembolic stroke (CE), noncardioembolic stroke with determined mechanism (NCE), or embolic stroke of undetermined source (ESUS). RESULTS: Over a 10-year (mean 9.7 years) follow-up period, 128 (5.8%) participants reached endpoint, including 46 with CE, 33 with NCE, and 49 with ESUS. Regardless of stroke subtype, LA expansion index was lower in the event groups compared to the nonevent group. The lowest quartile of LA expansion index was associated with high CHA2 DS2 -VASc score at enrollment and more events, including CE, ESUS, atrial fibrillation (AF), heart failure, and all-cause mortality, relative to other quartiles. The LA expansion index was an independent predictor of CE (HR 0.82; 95% CI 0.723-0.912, per 10% increase in LA expansion index; P < .0001) and ESUS (HR 0.92; 95% CI 0.881-0.976, per 10% increase in LA expansion index; p 0.003). An LA expansion index <68% predicts the presence of AF after ESUS with 84% sensitivity and 70% specificity. CONCLUSION: LA expansion index is useful for predicting CE and ESUS. It is also associated with AF, heart failure hospitalization, and all-cause mortality.

Pioglitazone reversed the fructose-programmed astrocytic glycolysis and oxidative phosphorylation of female rat offspring.

Excessive maternal high-fructose diet (HFD) during pregnancy and lactation has been reported to cause metabolic disorders in the offspring. Whether the infant's brain metabolism is disturbed by maternal HFD is largely unknown. Brain energy metabolism is elevated dramatically during fetal and postnatal development, whereby maternal nutrition is a key factor that determines cellular metabolism. Astrocytes, a nonneuronal cell type in the brain, are considered to support the high-energy demands of neurons by supplying lactate. In this study, the effects of maternal HFD on astrocytic glucose metabolism were investigated using hippocampal primary cultures of female infants. We found that glycolytic capacity and mitochondrial respiration and electron transport chain were suppressed by maternal HFD. Mitochondrial DNA copy number and mitochondrial transcription factor A expression were suppressed by maternal HFD. Western blots and immunofluorescent images further indicated that the glucose transporter 1 was downregulated whereas the insulin receptor-α, phospho-insulin receptor substrate-1 (Y612) and the p85 subunit of phosphatidylinositide 3-kinase were upregulated in the HFD group. Pioglitazone, which is known to increase astrocytic glucose metabolism, effectively reversed the suppressed glycolysis, and lactate release was restored. Moreover, pioglitazone also normalized oxidative phosphorylation with an increase of cytosolic ATP. Together, these results suggest that maternal HFD impairs astrocytic energy metabolic pathways that were reversed by pioglitazone.

Peripheral inflammation increases seizure susceptibility via the induction of neuroinflammation and oxidative stress in the hippocampus.

BACKGROUND: Neuroinflammation with activation of microglia and production of proinflammatory cytokines in the brain plays an active role in epileptic disorders. Brain oxidative stress has also been implicated in the pathogenesis of epilepsy. Damage in the hippocampus is associated with temporal lobe epilepsy, a common form of epilepsy in human. Peripheral inflammation may exacerbate neuroinflammation and brain oxidative stress. This study examined the impact of peripheral inflammation on seizure susceptibility and the involvement of neuroinflammation and oxidative stress in the hippocampus. RESULTS: In male, adult Sprague-Dawley rats, peripheral inflammation was induced by the infusion of Escherichia coli lipopolysaccharide (LPS, 2.5 mg/kg/day) into the peritoneal cavity for 7 days via an osmotic minipump. Pharmacological agents were delivered via intracerebroventricular (i.c.v.) infusion with an osmotic minipump. The level of cytokine in plasma or hippocampus was analyzed by ELISA. Redox-related protein expression in hippocampus was evaluated by Western blot. Seizure susceptibility was tested by intraperitoneal (i.p.) injection of kainic acid (KA, 10 mg/kg). We found that i.p. infusion of LPS for 7 days induced peripheral inflammation characterized by the increases in plasma levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). This is associated with a significant increase in number of the activated microglia (Iba-1(+) cells), enhanced production of proinflammatory cytokines (including IL-1ß, IL-6 and TNF-α), and tissue oxidative stress (upregulations of the NADPH oxidase subunits) in the hippocampus. These cellular and molecular responses to peripheral inflammation were notably blunted by i.c.v. infusion of a cycloxygenase-2 inhibitor, NS398 (5 µg/µl/h). The i.c.v. infusion of tempol (2.5 µg/µl/h), a reactive oxygen species scavenger, protected the hippocampus from oxidative damage with no apparent effect on microglia activation or cytokine production after peripheral inflammation. In the KA-induced seizure model, i.c.v. infusion of both NS398 and tempol ameliorated the increase in seizure susceptibility in animals succumbed to the LPS-induced peripheral inflammation. CONCLUSIONS: Together these results indicated that LPS-induced peripheral inflammation evoked neuroinflammation and the subsequent oxidative stress in the hippocampus, resulting in the increase in KA-induced seizure susceptibility. Moreover, protection from neuroinflammation and oxidative stress in the hippocampus exerted beneficial effect on seizure susceptibility following peripheral inflammation.

Transcriptional upregulation of mitochondrial uncoupling protein 2 protects against oxidative stress-associated neurogenic hypertension.

RATIONALE: Mitochondrial uncoupling proteins (UCPs) belong to a superfamily of mitochondrial anion transporters that uncouple ATP synthesis from oxidative phosphorylation and mitigates mitochondrial reactive oxygen species production. OBJECTIVE: We assessed the hypothesis that UCP2 participates in central cardiovascular regulation by maintaining reactive oxygen species homeostasis in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons that maintain vasomotor tone located. We also elucidated the molecular mechanisms that underlie transcriptional upregulation of UCP2 in response to oxidative stress in RVLM. METHODS AND RESULTS: In Sprague-Dawley rats, transcriptional upregulation of UCP2 in RVLM by rosiglitazone, an activator of its transcription factor peroxisome proliferator-activated receptor (PPAR)gamma, reduced mitochondrial hydrogen peroxide level in RVLM and systemic arterial pressure. Oxidative stress induced by microinjection of angiotensin II into RVLM augmented UCP2 mRNA or protein expression in RVLM, which was antagonized by comicroinjection of NADPH oxidase inhibitor (diphenyleneiodonium chloride), superoxide dismutase mimetic (tempol), or p38 mitogen-activated protein kinase inhibitor (SB203580) but not by extracellular signal-regulated kinase 1/2 inhibitor (U0126). Angiotensin II also induced phosphorylation of the PPARgamma coactivator, PPARgamma coactivator (PGC)-1alpha, and an increase in formation of PGC-1alpha/PPARgamma complexes in a p38 mitogen-activated protein kinase-dependent manner. Intracerebroventricular infusion of angiotensin II promoted an increase in mitochondrial hydrogen peroxide production in RVLM and chronic pressor response, which was potentiated by gene knockdown of UCP2 but blunted by rosiglitazone. CONCLUSIONS: These results suggest that transcriptional upregulation of mitochondrial UCP2 in response to an elevation in superoxide plays an active role in feedback regulation of reactive oxygen species production in RVLM and neurogenic hypertension associated with chronic oxidative stress.

Sensory nerve conduction studies of the superficial peroneal nerve in L5 radiculopathy.

BACKGROUND: Theoretically, sensory nerve action potential (SNAP) of the superficial peroneal nerve (SPN) should be preserved when L5 roots are damaged. Previous study indicated that SNAP of SPN was lost or reduced in amplitude in patiens with L5 radiculopathy. To address this issue, this study compared results of SPN sensory conduction studies between healthy subjects and patients with L5 radiculopathy. METHODS: Ninety-four healthy subjects were enrolled and assigned to two age groups: group I (< or = 60 years, n=61) and group II (> 60 years, n=33). Forty-one patients with unilateral L5 radiculopathy were enrolled by our electrodiagnostic laboratory between July 2000 and July 2003 and assigned to two age groups: 60 years or below (n=19) and above 60 years (n=22). RESULTS: SPN response was found to be abnormal in only 1.6% of group I healthy subjects, but absent or abnormal SPN response was noted in 21.1% of patients with L5 radiculopathy of the same age group (p=0.01). However, a greater proportion of (27.3%) our healthy subjects above 60 years had abnormal SPN responses. This proportion was similar to that of patients with L5 radiculopathy and abnormal SPN response (31.8%) (p=0.72). CONCLUSIONS: SPN sensory responses are reliably obtained in most healthy subjects under 60 years of age. Absence of SNAP or reduced SNAP amplitude of SPN on the side of their lesions did not necessarily exclude the diagnosis of L5 radiculopathy in the patients under 60 years of age.