Pharmacological disruption of the interaction between fibrinogen and β-amyloid reduces vascular amyloid deposition and improves cognition in a mouse model of Alzheimer’s disease.

No abstract

Summary: Neurological complications of hypoglycemia often include seizures and fasting is a predisposing factor for seizures to occur. The mechanisms involved are unknown. In rats, insulin administration induces hypoglycemia, which may lead to generalized seizures with barrel rotations as a hallmark. Here we compared the incidence of barrel rotations in fasted and nonfasted rats. Further, we investigated the role of the substantia nigra pars reticulata (SNR) in control of barrel rotations using localized bilateral microinfusions of GABA A or GABA B receptor agonists (muscimol or baclofen, respectively) or an N-methyl-D-aspartate (NMDA) receptor antagonist (AP7). The incidence of barrel rotations was significantly higher in fasted compared to nonfasted rats. SNR infusions of muscimol were ineffective, while both baclofen and AP7 significantly decreased occurrence of barrel rotations. These data suggest that during hypoglycemia, the SNR seizure controlling system has different properties than in seizure models not involving a metabolic stress. Key Words: Hypoglycemia-Fasting-Seizure-Barrel rotationSubstantia nigra-GABA.Glucose is the main source of energy for neurons and changes in glucose levels alter brain function. Hypoglycemia commonly occurs in patients with diabetes mellitus as a side effect of insulin treatment (Herbel and Boyle, 2000), or in hyperinsulinism due to insulinoma (Malouf and Brust, 1985), and it is a critical problem in the management of these diseases. Hypoglycemia presents with a variety of neurological impairments, interferes with everyday life, and creates a serious psychological burden for the patient. Seizures are one of the most common acute symptoms (Malouf and Brust, 1985). To better understand the neurologic complications, animal models have been used. In rats, insulin administration induces hypoglycemia, which may lead to generalized seizures with barrel rotations as the main feature (Gastaut et al., 1968).The substantia nigra pars reticulata (SNR) has been identified as a critical midbrain structure involved in motor control and modulation of seizures (Iadarola and Gale, 1982;Depaulis et al., 1994;Velíšková and Moshé, 2006). The SNR contains mainly GABAergic neurons with high spontaneous firing rates. The seizure control is achieved when the activity of the SNR GABAergic neurons is decreased. Thus, focal enhancement of GABA-mediated in- hibitory effects by localized bilateral SNR microinfusions of muscimol (a GABA A receptor agonist) have anticonvulsant effects in several models of generalized seizures (Iadarola and Gale, 1982;Depaulis et al., 1994;Velíšková and Moshé, 2006). Similarly, treatments that decrease the excitatory glutamatergic neurotransmission in the SNR, such as infusions of AP7 (an NMDA receptor antagonist) also have anticonvulsant effects (Wurpel et al., 1992;. Since fasting or irregular food intake are predisposing factors for seizure expression during hypoglycemic crises in humans (Malouf and Brust, 1985), here we used an animal model to investigate the incidence ...