Daily Anesthesiology Research Analysis

Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure and dural venous sinus stenoses, which can be relieved by venous stenting. Here we investigated whether venous blood flow may play a role in controlling brain pressure. Using magnetic resonance imaging in patients with IIH and healthy controls, we identified that dural venous stenoses in IIH were associated with alterations of the perivenous fluid pattern and brain edema. We developed a mouse model of jugular vein ligation (JVL), which developed transient intracerebral hypertension, brain edema and impaired brain clearance, along with defective meningeal lymphatic vessels (MLVs). MLV depletion increased intracerebral pressure in control and JVL mice, but only MLV-deficient ligated mice failed to restore brain fluid clearance. These findings implicate MLVs in the control of intracerebral pressure and establish the dural venous sinuses as critical platforms where venous flow directs MLVs to ensure brain fluid clearance.

Perioperative neurocognitive disorders (PND), highly prevalent in geriatric surgical populations, constitute a major postoperative clinical challenge associated with prolonged hospital stays and adverse surgical outcomes. Although substantial research efforts have been devoted to investigating etiology, the precise molecular mechanisms of PND remains elusive, thereby hindering the development of effective therapeutic interventions. To address this gap, we conducted single-nucleus RNA sequencing on 119,109 hippocampal cells isolated from 18-month-old PND mice and age-matched controls, alongside performing complementary Western blotting and electrophysiological experiments. We propose that hippocampal neuronal excitation-inhibition (E/I) imbalance serves as a key mechanism underlying PND, which is associated with dysregulated inhibitory control of excitatory plasticity in PND pathology. Furthermore, we identified PND-associated astrocytes and oligodendrocytes-distinct from those in other cognitive disorders and linked to E/I imbalance. These cell types played distinct roles in the pathological process of PND. Our study proposes that E/I imbalance, associated with dysregulated inhibitory control of excitatory plasticity, underlies the pathogenesis of PND, providing new insights for therapeutic interventions.

Temporomandibular disorders (TMD) pain is the most common orofacial pain with limited effective treatments. Here, we observed elevated lysophosphatidic acid (LPA), a bioactive lipid, in blood, trigeminal ganglion (TG), and peri-temporomandibular joint (TMJ) tissues in mouse models of TMD-like pain induced by TMJ inflammation or masseter muscle injury. Notably, LPA levels were also elevated in TMD patients' blood and positively correlated with their pain intensity. LPA receptors (LPAR) 1 and 3 were expressed in mouse and human TG neurons and upregulated in TMD-like pain models. Inhibition or knockout of LPAR1 or LPAR3 attenuated TMD-like pain, while LPA injection into the TMJ or masseter muscle evoked pain. Furthermore, we demonstrated that LPA/LPAR signaling upregulates and sensitizes PIEZO2, a mechanosensitive ion channel, in TG neurons via extracellular signal-regulated kinase (ERK). Specific deletion or inhibition of PIEZO2 and suppression of ERK activation in TG neurons mitigated TMD-like pain. These findings suggest that LPA/LPAR signaling drives TMD-like pain via PIEZO2, offering potential therapeutic targets.