Comparison of Local and Systemic Inflammation During Invasive Versus Noninvasive Ventilation in Rats.

The impact of noninvasive ventilation (NIV) on local and systemic inflammation is poorly characterized, particularly when compared with invasive mechanical ventilation (IMV). We sought to quantify the local and systemic inflammatory response of these 2 respiratory treatments in rats with lipopolysaccharide (LPS)-induced lung injury (LPS-injured) and healthy rats. Animals were subjected to 4 h of NIV or IMV treatments at noninjurious settings, or 4 h of control treatment in which healthy or LPS-injured animals remained spontaneously breathing under isoflurane anesthesia with no respiratory support. Cytokines were then quantified in the serum and lung tissue by multiplex enzyme-linked immunosorbent assay. Contrary to our hypothesis, there were no significant differences in cytokine levels in serum or lung when comparing the NIV- and IMV-treated groups; this was true in both LPS-injured and healthy rats. However, within the LPS-injured group, pulmonary levels of interleukin (IL)-1α, IL-6, and tumor necrosis factor α were significantly lower in the NIV-treated group than in control but not in the IMV-treated group compared with control. We conclude that NIV, unlike IMV, could attenuate local inflammation.

Cosyntropin Attenuates Neuroinflammation in a Mouse Model of Traumatic Brain Injury.

Aim: Traumatic brain injury (TBI) is a leading cause of mortality/morbidity and is associated with chronic neuroinflammation. Melanocortin receptor agonists including adrenocorticotropic hormone (ACTH) ameliorate inflammation and provide a novel therapeutic approach. We examined the effect of long-acting cosyntropin (CoSyn), a synthetic ACTH analog, on the early inflammatory response and functional outcome following experimental TBI. Methods: The controlled cortical impact model was used to induce TBI in mice. Mice were assigned to injury and treatment protocols resulting in four experimental groups including sham + saline, sham + CoSyn, TBI + saline, and TBI + CoSyn. Treatment was administered subcutaneously 3 h post-injury and daily injections were given for up to 7 days post-injury. The early inflammatory response was evaluated at 3 days post-injury through the evaluation of cytokine expression (IL1ß and TNFα) and immune cell response. Quantification of immune cell response included cell counts of microglia/macrophages (Iba1+ cells) and neutrophils (MPO+ cells) in the cortex and hippocampus. Behavioral testing (n = 10-14 animals/group) included open field (OF) and novel object recognition (NOR) during the first week following injury and Morris water maze (MWM) at 10-15 days post-injury. Results: Immune cell quantification showed decreased accumulation of Iba1+ cells in the perilesional cortex and CA1 region of the hippocampus for CoSyn-treated TBI animals compared to saline-treated. Reduced numbers of MPO+ cells were also found in the perilesional cortex and hippocampus in CoSyn treated TBI mice compared to their saline-treated counterparts. Furthermore, CoSyn treatment reduced IL1ß expression in the cortex of TBI mice. Behavioral testing showed a treatment effect of CoSyn for NOR with CoSyn increasing the discrimination ratio in both TBI and Sham groups, indicating increased memory performance. CoSyn also decreased latency to find platform during the early training period of the MWM when comparing CoSyn to saline-treated TBI mice suggesting moderate improvements in spatial memory following CoSyn treatment. Conclusion: Reduced microglia/macrophage accumulation and neutrophil infiltration in conjunction with moderate improvements in spatial learning in our CoSyn treated TBI mice suggests a beneficial anti-inflammatory effect of CoSyn following TBI.

Preparation of Rhythmically-active In Vitro Neonatal Rodent Brainstem-spinal Cord and Thin Slice.

Mammalian inspiratory rhythm is generated from a neuronal network in a region of the medulla called the preBötzinger complex (pBC), which produces a signal driving the rhythmic contraction of inspiratory muscles. Rhythmic neural activity generated in the pBC and carried to other neuronal pools to drive the musculature of breathing may be studied using various approaches, including en bloc nerve recordings and transverse slice recordings. However, previously published methods have not extensively described the brainstem-spinal cord dissection process in a transparent and reproducible manner for future studies. Here, we present a comprehensive overview of a method used to reproducibly cut rhythmically-active brainstem slices containing the necessary and sufficient neuronal circuitry for generating and transmitting inspiratory drive. This work builds upon previous brainstem-spinal cord electrophysiology protocols to enhance the likelihood of reliably obtaining viable and rhythmically-active slices for recording neuronal output from the pBC, hypoglossal premotor neurons (XII pMN), and hypoglossal motor neurons (XII MN). The work presented expands upon previous published methods by providing detailed, step-by-step illustrations of the dissection, from whole rat pup, to in vitro slice containing the XII rootlets.