Inflammatory pathways are central to posterior cerebrovascular artery remodelling prior to the onset of congenital hypertension

Cerebral artery hypoperfusion may provide the basis for linking ischemic stroke with hypertension. Brain hypoperfusion may induce hypertension that may serve as an auto-protective mechanism to prevent ischemic stroke. We hypothesised that hypertension is caused by remodelling of the cerebral arteries, which is triggered by inflammation. We used a congenital rat model of hypertension and examined age-related changes in gene expression of the cerebral arteries using RNA sequencing. Prior to hypertension, we found changes in signalling pathways associated with the immune system and fibrosis. Validation studies using second harmonics generation microscopy revealed upregulation of collagen type I and IV in both tunica externa and media. These changes in the extracellular matrix of cerebral arteries pre-empted hypertension accounting for their increased stiffness and resistance, both potentially conducive to stroke. These data indicate that inflammatory driven cerebral artery remodelling occurs prior to the onset of hypertension and may be a trigger elevating systemic blood pressure in genetically programmed hypertension. </jats:p

Glycine induces a novel form of long-term potentiation in the superficial layers of the superior colliculus

1. The mammalian superior colliculus (SC) is a midbrain nucleus containing space maps of different sensory modalities which show various forms of age- and activity-dependent plasticity in vivo and in vitro. In the present study, we aimed to characterize the role of glycine (Gly) receptors in the SC, and we observed that application of glycine (Gly; 500 μM and 3 mM) for 7 min to SC slices of adult guinea-pigs caused a novel form of long-term potentiation (termed LTP(gly)) of evoked excitatory postsynaptic potentials recorded in the superficial layers. 2. The strength of potentiation was found to be concentration-dependent and partially independent from synaptic stimulation. 3. LTP(gly) did not involve NMDA receptor activation as proven by the lack of inhibition by 100 μM D,L-2-amino-5-phosphonovaleric acid (APV) and 10 μM MK-801. 4. LTP(gly) could only be masked but not prevented by strychnine (100 μM) and remained undisturbed in the presence of picrotoxin (100 μM). 5. Inhibition of carbonic anhydrase by acetazolamide (20 μM) had no effect on LTP(gly) suggesting that the excitatory action of Gly is not due to a differential breakdown of the Cl(−)/HCO(3)(−) gradients. 6. As indicated by the inhibition of LTP(gly) of the fEPSP slope by the L-type calcium channel blocker nifedipine (20 μM), voltage-dependent calcium channels are the source for Ca(2+) elevation as the intracellular trigger. 7. Our data provide the first evidence for a role of Gly in SC synaptic transmission. They illustrate a so far unknown action of Gly which can lead to long-lasting changes of synaptic efficacy and which is not mediated via NMDA-related or strychnine-sensitive binding sites