Researchers mapped special brain structures called perineuronal nets (PNNs) in a part of the brain that controls blood pressure. They found that in male mice with a type of high blood pressure, these nets become more abundant, especially around certain neurons, which may make the brain area more excitable. Oxytocin‑related neurons showed some sex differences, but the study didn’t test oxytocin as a treatment.

Perineuronal nets (PNNs) are key regulators of neuronal excitability, yet whether they are altered during neurogenic hypertension is unknown. Here, we mapped the developmental trajectory of PNNs in the paraventricular nucleus of the hypothalamus (PVN), a crucial nucleus involved in blood pressure (BP) regulation, and examined their modulation in neurogenic hypertension. We show that PNNs in the PVN follow a developmental pattern similar to other brain regions. The most prevalent neuron subtype enwrapped by PNNs was neuronal nitric oxide synthase (nNOS)-expressing neurons in both sexes, and sex differences were observed only in oxytocin (OXT)-enwrapped neurons. In the DOCA-salt mouse model of neurogenic hypertension, males, but not females, exhibit an increased number and area of PNNs in the PVN with increased excitatory/inhibitory (E/I) ratio. Given that PNNs modulate neuronal activity, our findings may implicate recruitment of previously "silent" neurons as potential contributors of PVN hyperactivity in hypertension. These results demonstrate that PNN remodeling is associated with neurogenic hypertension in male mice.