Pathogenesis and Diagnosis of Proximal Hamstring Tendinopathies.

The proximal hamstring complex is a highly vulnerable area that is especially prone to injury. Proximal hamstring tendinopathies (PHTs) remain challenging in diagnosis, treatment, rehabilitation, and prevention due to a large variety of different injuries, slow healing response, persistent symptoms, and functional impairments. PHTs are often misdiagnosed or underdiagnosed, leading to delayed treatment and therapy failure. In addition, many athletes are at a high risk of PHT recurrence, a leading cause of prolonged rehabilitation and impaired individual performance. Until now, there have been no clear criteria for the diagnosis and classification of PHT. Tendinopathies can be graded based on their symptoms and onset. Additionally, radiological characteristics exist that describe the severity of tendinopathies. The diagnosis usually includes a battery of pain provocation tests, functional tests, and imaging to ensure a proper classification. Understanding the specific tasks in the pathogenesis and diagnostic process of PHT requires knowledge of functional anatomy, injury pattern and pathophysiological mechanisms as well as examination and imaging techniques. This work provides a structured overview of the pathogenesis and diagnostic work-up of PHT, emphasizing structured examination and imaging to enable a reliable diagnosis and rapid treatment decisions.

Effects of exercise and cold-water exposure on microvascular muscle perfusion.

PURPOSE: Microvascular blood flow (MBF) and its intramuscular regulation are of importance for physiological responsiveness and adaptation. The quantifiable in-vivo monitoring of MBF after cycling or systemic cold-water exposure may reveal new insights into capillary regulatory mechanisms. This study aimed to assess the role of exercise and cold therapy on MBF by using contrast-enhanced ultrasound (CEUS). METHODS: Twenty healthy athletes were recruited and randomly assigned to an intervention (IG) or a control group (CG). MBF was quantified in superficial (rectus femoris, RF) and deep muscle layers (vastus intermedius, VI). Representative perfusion parameters (peak enhancement (PE) and wash-in area under the curve (WiAUC)) were measured after a standardized measurement protocol for both groups at resting conditions (t0) and after cycling (20 min., 70% Watt max, t1) for both groups, after cold-water immersion exposure for IG (15 min., 12°C) or after precisely 15 minutes of rest for CG (t2) and for both groups after 60 minutes of follow-up (t3). RESULTS: At t1, MBF in VI increased significantly compared to resting conditions in both groups in VI (p= 0.02). After the cold-water exposure (t2), there were no statistically significant changes in perfusion parameters as well as after 60 minutes of follow-up (t3) (p = 0.14). CONCLUSION: Cycling leads to an upregulation of MBF. However, cold exposure does not change the MBF. The implementation of CEUS during different physiological demands may provide deeper insight into intramuscular perfusion regulation and regenerative processes.

Real-time imaging of glutamate transients in the extracellular space of acute human brain slices using a single-wavelength glutamate fluorescence nanosensor.

Glutamate is the most important excitatory neurotransmitter in the brain. The ability to assess glutamate release and re-uptake with high spatial and temporal resolution is crucial to understand the involvement of this primary excitatory neurotransmitter in both normal brain function and different neurological disorders. Real-time imaging of glutamate transients by fluorescent nanosensors has been accomplished in rat brain slices. We performed for the first time single-wavelength glutamate nanosensor imaging in human cortical brain slices obtained from patients who underwent epilepsy surgery. The glutamate fluorescence nanosensor signals of the electrically stimulated human cortical brain slices showed steep intensity increase followed by an exponential decrease. The spatial distribution and the time course of the signal were in good agreement with the position of the stimulation electrode and the dynamics of the electrical stimulation, respectively. Pharmacological manipulation of glutamate release and reuptake was associated with corresponding changes in the glutamate fluorescence nanosensor signals. We demonstrated that the recently developed fluorescent nanosensors for glutamate allow to detect neuronal activity in acute human cortical brain slices with high spatiotemporal precision. Future application to tissue samples from different pathologies may provide new insights into pathophysiology without the limitations of an animal model.

Glucocorticoid modulation of synaptic plasticity in the human temporal cortex of epilepsy patients: Does chronic stress contribute to memory impairment?

OBJECTIVE: Memory impairment is common in patients with temporal lobe epilepsy and seriously affects life quality. Chronic stress is a recognized cofactor in epilepsy and can also impair memory function. Furthermore, increased cortisol levels have been reported in epilepsy patients. Animal models have suggested that aggravating effects of stress on memory and synaptic plasticity were mediated via glucocorticoids. The aim of this study was, therefore, to investigate the effect of glucocorticoid receptor (GR) modulation on synaptic plasticity in the human cortex of epilepsy patients. METHODS: We performed field potential recordings in acute slices from the temporal neocortex of patients who underwent surgery for drug-resistant temporal lobe epilepsy. Synaptic plasticity was investigated by a theta-burst stimulation (TBS) protocol for induction of long-term potentiation (LTP) in the presence of GR modulators. RESULTS: LTP was impaired in temporal cortex from epilepsy patients. Pretreatment of the slices with the GR antagonist mifepristone (RU486) improved LTP induction, suggesting that LTP impairment was due to baseline GR activation in the human cortex. The highly potent GR agonist dexamethasone additionally weakened synaptic strength in an activity-dependent manner when applied after TBS. SIGNIFICANCE: Our results show a direct negative glucocorticoid effect on synaptic potentiation in the human cortex and imply chronic activation of GRs. Chronic stress may therefore contribute to memory impairment in patients with temporal lobe epilepsy. Furthermore, the activity-dependent acute inhibitory effect of dexamethasone suggests a mechanism of synaptic downscaling by which postictally increased cortisol levels may prevent pathologic plasticity upon seizures.