Trajectory of Parvalbumin Cell Impairment and Loss of Cortical Inhibition in Traumatic Brain Injury.

Many neuropsychiatric symptoms that follow traumatic brain injury (TBI), including mood disorders, sleep disturbance, chronic pain, and posttraumatic epilepsy (PTE) are attributable to compromised cortical inhibition. However, the temporal trajectory of cortical inhibition loss and its underlying mechanisms are not known. Using paired-pulse transcranial magnetic stimulation (ppTMS) and immunohistochemistry, we tracked functional and cellular changes of cortical inhibitory network elements after fluid-percussion injury (FPI) in rats. ppTMS revealed a progressive loss of cortical inhibition as early as 2 weeks after FPI. This profile paralleled the increasing levels of cortical oxidative stress, which was accompanied by a gradual loss of parvalbumin (PV) immunoreactivity in perilesional cortex. Preceding the PV loss, we identified a degradation of the perineuronal net (PNN)-a specialized extracellular structure enwrapping cortical PV-positive (PV+) inhibitory interneurons which binds the PV+ cell maintenance factor, Otx2. The trajectory of these impairments underlies the reduced inhibitory tone, which can contribute to posttraumatic neurological conditions, such as PTE. Taken together, our results highlight the use of ppTMS as a biomarker to track the course of cortical inhibitory dysfunction post-TBI. Moreover, the neuroprotective role of PNNs on PV+ cell function suggests antioxidant treatment or Otx2 enhancement as a promising prophylaxis for post-TBI symptoms.

Evaluation of therapeutic control in a Pakistani population with hypertension.

RATIONALE, AIMS AND OBJECTIVES: Cardiovascular diseases (CVD) are increasing at an alarming rate in South Asia. High blood pressure is a modifiable risk factor for CVD. In this study, we evaluated the control of blood pressure and the prevalence of cardiovascular risk factors in patients with hypertension. METHOD: A cross-sectional study was conducted in 50 primary health care centres throughout Pakistan. Individuals with a documented history of hypertension, receiving pharmacological therapy, were enrolled and evaluated for the control of their blood pressure. RESULTS: The recommended therapeutic control of hypertension (systolic blood pressure <140 mmHg, diastolic blood pressure <90 mmHg) was seen in only 6.4% of the study participants. Values of both the mean systolic and diastolic blood pressures in all subjects were higher than the desired therapeutic levels (P<0.001). There was a high prevalence in the study population of established but modifiable risk factors of CVD, such as smoking (30.5%), hypercholesterolemia (59.5%) and sedentary lifestyle (43.5%). Lack of therapeutic control of systolic blood pressure was found significantly associated with age, hypercholesterolemia and sedentary lifestyle (P<0.05). CONCLUSIONS: Patients being treated at primary health care centres in Pakistan have inadequate control of high blood pressure. Evidence-based continuous education of primary health care physicians is a necessary intervention for optimizing treatment strategies and achieving better therapeutic control of hypertension in our population.