The Effect of High-Salt Diet on Oxidative Stress Production and Vascular Function in Tff3-/-/C57BL/6N Knockout and Wild Type (C57BL/6N) Mice.

INTRODUCTION: It is well documented that high-salt (HS) diet increases systemic and vascular oxidative stress in various animal models and in humans, leading to impairment of vascular reactivity. The present study examined the interaction of genotype and HS diet intake and the potential effects of oxidative stress - antioxidative system balance on the flow-induced dilation (FID) in pressurized carotid arteries of normotensive Tff3-/-/C57BL/6N knockout mice and their wild-type (WT) controls. METHODS: Male, ten-week-old transgenic Tff3-/-/C57BL/6N (Tff3-/-) knockout mice and WT/C57BL/6N (WT) (parental strain) healthy mice were divided in LS (0.4% NaCl in rodent chow) and HS (4% NaCl in rodent chow fed for 1 week) groups. Additionally, LS and HS groups were treated with 1 mmol/L 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) dissolved in the drinking water. After anesthesia with ketamine chloride (100 mg/kg) and midazolam (5 mg/kg), blood pressure was measured, carotid arteries and aortas were isolated, and blood samples were collected. RESULTS: FID was decreased in WT_HS mice and restored by superoxide scavenger TEMPOL in vivo. On the other hand, attenuated FID of Tff3-/- mice was not further affected by HS diet or TEMPOL in vivo treatment. Vascular superoxide/reactive oxygen species levels were increased with HS diet in both strains and restored by TEMPOL. HS upregulated glutathione peroxidase 1 (GPx1) gene expression in WT_HS and Tff3-/-_HS mice, while GPx activity was significantly decreased only in WT_HS group. Systemic (serum) markers of oxidative stress (oxLDL and AOPP) and arterial blood pressure were similar among groups. CONCLUSION: HS diet increases vascular oxidative stress and impairs vasodilation in WT mice. Tff3 gene deficiency attenuates vasodilation per se, without further effects of HS intake. This can be attributed to vascular upregulation of antioxidative enzyme GPx1 in Tff3-/-/C57BL/6N mice conferring protection from oxidative stress.

Role of uroguanylin's signalling pathway in the development of ischaemic stroke.

Stroke is one of the leading causes of mortality and disability worldwide. By affecting bradykinin function, activation of guanylate cyclase (GC)-A has been shown to have a neuroprotective effect after ischaemic stroke, whereas the same has not been confirmed for GC-B; therefore, we aimed to determine the possible role of GC-C and its agonist, uroguanylin (UGN), in the development of stroke. In this study, middle cerebral artery occlusion (MCAO) was performed on wild-type (WT), GC-C KO and UGN KO mice. MR images were acquired before and 24 h after MCAO. On brain slices 48 h after MCAO, the Ca2+ response to UGN stimulation was recorded. Our results showed that the absence of GC-C in GC-C KO mice resulted in the development of smaller ischaemic lesions compared with WT littermates, which is an opposite effect compared with the effects of GC-A agonists on brain lesions. WT and UGN KO animals showed a stronger Ca2+ response upon UGN stimulation in astrocytes of the peri-ischaemic cerebral cortex compared with the same cortical region of the unaffected contralateral hemisphere. This stronger activation was not observed in GC-C KO animals, which may be the reason for smaller lesion development in GC-C KO mice. The reason why GC-C might affect Ca2+ signalling in peri-ischaemic astrocytes is that GC-C is expressed in these cells after MCAO, whereas under normoxic conditions, it is expressed mainly in cortical neurons. Stronger activation of the Ca2+ -dependent signalling pathway could lead to the stronger activation of the Na+ /H+ exchanger, tissue acidification and neuronal death.

Microglia and bradykinin cross talk in poststroke cognitive impairment in diabetes.

Stroke is one of the leading causes of mortality and the leading cause of long-term disability worldwide. Although cognitive impairment is a common consequence of stroke, the underlying pathophysiological processes that lead to it are still poorly understood. Recently, more studies have shown evidence of the involvement of diabetes in producing a chronic neuroinflammatory state, which ultimately alters the recovery of function and cognition after stroke. To better understand the impact of diabetes on poststroke recovery, here we highlight the recent insights on the role of diabetes in neuroinflammation, especially regarding its effect on microglial function, and the emerging data on the involvement of kinins in both diabetes and neuroinflammation.

The Impact of Fascial Manipulation® on Posterior Shoulder Tightness in Asymptomatic Handball Players: A Randomized Controlled Trial.

This prospective study aimed to determine the impact of Fascial Manipulation® by Stecco (FM) on the range of motion (ROM) of internal rotation (IR) and horizontal adduction (HADD) in asymptomatic handball players, representing significant risk factors for shoulder injuries. A randomized controlled trial was conducted, with participants randomly assigned to either the investigated group (N = 29) receiving a single session of FM or the control group (N = 27) receiving no treatment. The ROM for IR and HADD were measured before, immediately after, and one month after the FM session. The investigated group experienced a statistically significant acute increase in glenohumeral IR (14 degrees, p < 0.001) and HADD (14 degrees, p < 0.001) compared to the control group (p < 0.001). The positive effects of FM persisted one month post-treatment, with increased IR ROM by 12 degrees (p < 0.001) and HADD ROM by 11 degrees (p < 0.001). Participants in the investigated group reported lower subjective tightness/stiffness immediately after (p < 0.001) and one month after treatment (p = 0.002) compared to the control group. This study demonstrates that a single application of FM effectively improves glenohumeral ROM in the dominant throwing shoulder of asymptomatic handball players. It highlights the immediate and sustained positive effects of FM on IR and HADD. These findings support the use of FM as an effective method for enhancing shoulder ROM and reducing subjective tightness/stiffness. The study was registered at ClinicalTrials.gov (NCT06009367).

The temporal dynamic of bradykinin type 2 receptor effects reveals its neuroprotective role in the chronic phase of cerebral and retinal ischemic injury.

The activation of the bradykinin type 2 receptor is intricately involved in acute post-ischemic inflammatory responses. However, its precise role in different stages of ischemic injury, especially in the chronic phase, remains unclear. Following simultaneous cerebral and retinal ischemia, bradykinin type 2 receptor knockout mice and their controls were longitudinally monitored for 35 days via magnetic resonance imaging, fundus photography, fluorescein angiography, behavioral assessments, vascular permeability measurements, and immunohistochemistry, as well as glycemic status assessments. Without impacting the lesion size, bradykinin type 2 receptor deficiency reduced acute cerebral vascular permeability preventing the loss of pericytes and tight junctions. In the chronic phase of ischemia, however, it resulted in increased astrogliosis and cortical neuronal loss, as well as higher functional deficits. The retinal findings demonstrated a similar pattern. Bradykinin type 2 receptor deficiency delayed, but exacerbated the development of retinal necrosis, increased subacute vascular permeability, and promoted retinal ganglion cell loss in the chronic phase of ischemia. This investigation sheds light on the temporal dynamic of bradykinin type 2 receptor effects in ischemia, pointing to a therapeutic potential in the subacute and chronic phases of ischemic injury.

Redefining the Koizumi model of mouse cerebral ischemia: A comparative longitudinal study of cerebral and retinal ischemia in the Koizumi and Longa middle cerebral artery occlusion models.

Cerebral and retinal ischemia share similar pathogenesis and epidemiology, each carrying both acute and prolonged risk of the other and often co-occurring. The most used preclinical stroke models, the Koizumi and Longa middle cerebral artery occlusion (MCAO) methods, have reported retinal damage with great variability, leaving the disruption of retinal blood supply via MCAO poorly investigated, even providing conflicting assumptions on the origin of the ophthalmic artery in rodents. The aim of our study was to use longitudinal in vivo magnetic resonance assessment of cerebral and retinal vascular perfusion after the ischemic injury to clarify whether and how the Koizumi and Longa methods induce retinal ischemia and how they differ in terms of cerebral and retinal lesion evolution. We provided anatomical evidence of the origin of the ophthalmic artery in mice from the pterygopalatine artery. Following the Koizumi surgery, retinal responses to ischemia overlapped with those in the brain, resulting in permanent damage. In contrast, the Longa method produced only extensive cerebral lesions, with greater tissue loss than in the Koizumi method. Additionally, our data suggests the Koizumi method should be redefined as a model of ischemia with chronic hypoperfusion rather than of ischemia and reperfusion.

Epidemiology of injuries in female and male senior Slovenian handball leagues.

BACKGROUND: Handball is associated with a high frequency of injuries due to unexpected situations, external disturbances of movement and extreme positions of body segments. The purpose of this study was to identify and analyze injuries among female and male players from all five senior Slovenian handball leagues in the season 2010/2011. METHODS: We conducted a retrospective epidemiological study using a questionnaire. Data were collected between February and May 2012. Descriptive analysis is provided. RESULTS: Forty-five percent of all the players were injured, reporting 92 injuries. 0.58 injuries/player occurred, 57 (62%) in females and 35 (38%) in males. Injury incidence in females (27.7 injuries/1000 hours match, 0.97 injuries/1000 hours training) was higher than in men (10.6 injuries/1000 hours match, 0.5 injuries/1000 hours training), respectively. The left- and right-back players were injured most often (41%). Sprain was the most common injury type (55%). Most injuries were severe (29%). The lower limb was injured most frequently (62%). Ankle was injured the most commonly (35%), but ankle injuries were in most cases moderate (38%). More than 70% of knee injuries and 50% of shoulder injuries were severe. In 33%, cause of injury was contact with an opponent/teammate. Thirty-six percent of players reported shoulder and 36% ankle overuse syndromes. CONCLUSIONS: Present findings showed a higher incidence of injuries in female than in male senior Slovenian handball players in the 2010/2011 season. Preventive programs should focus not only on the acute ankle and knee injuries, but also on overuse syndromes of the shoulder and ankle.