Suppressed cytokine expression immediatey following traumatic brain injury in neonatal rats indicates an expeditious endogenous anti-inflammatory response

Abstract

The timing of therapeutic intervention in traumatic brain injury (TBI) is critical. Although immediate cell death cascades have become established in adult TBI, the pathophysiology underlying neonatal TBI is poorly understood. The objective of the present study was to determine the role of cytokine regulation following TBI in neonatal rats. Seven-day-old Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Age-matched littermates that did not receive TBI served as the controls. Immediately following TBI, rats were euthanized, and the brains were divided into the ipsilateral and contralateral hemispheres then flash frozen. A BioRad 23-Plex panel was used to measure cytokine levels. Surprisingly, the data revealed that 18 of the 23 cytokines analyzed were significantly downregulated in the hemisphere contralateral to the TBI impacted hemisphere. IL-5, IL-6 and MIP-3a were significantly suppressed in both ipsilateral and contralateral hemispheres of neonatal TBI rats compared to the control rats. A parallel study processing the plasma of the same cohort of neonatal rats revealed no difference in the same cytokines analyzed in the brain tissue, suggesting highly localized cytokine suppression in the brain during early injury. In stark contrast to the reported early pro-inflammatory response exhibited in adult TBI, the present neonatal TBI study demonstrated a reversed cytokine profile of downregulation. These results suggest a robust, immediate anti-inflammatory response mounted by the contralateral hemisphere of the young brain.

Treating childhood traumatic brain injury with autologous stem cell therapy

“…The most common causes of childhood TBI are falls or drops (64% of ER visits), car crashes (40% of deaths in young children), and shaken baby syndrome (in infants 6 months or younger) [1]. A serious condition that may result from TBI is HIE, which presents as a malfunction of or damage to the brain caused by the obstruction of oxygenated blood flow and occurs in about 2.5/1000 normal births [1, 2]. With newborns, HIE causes severe neurological deficits and may prompt doctors to subject the babies to hypothermia [3].…”

“…The most common form of stem cell therapy is the use of blood stem cells derived from the bone marrow to treat diseases and conditions of the blood and immune system [4]. Types of stem cells include embryonic, fetal, neonatal (e.g., placenta, umbilical cord blood and tissues, amnion fluid and tissues, Wharton jelly), and adult tissues [1–3]. Embryonic stem cells are derived from the inner cell mass of a blastocyst, an early stage of embryonic development [4].…”

“…Additionally, different approaches to transplant stem cells in CNS disorders have been investigated. Autologous transplantation refers to a process by which stem cells are harvested from a patient than later returned to the patient for treatment [1, 4]. Allogeneic transplants differ in that stem cells are harvested from a donor (with similar immune system markers to the recipient) and transplanted to the recipient [1, 4].…”

“…Autologous transplantation refers to a process by which stem cells are harvested from a patient than later returned to the patient for treatment [1, 4]. Allogeneic transplants differ in that stem cells are harvested from a donor (with similar immune system markers to the recipient) and transplanted to the recipient [1, 4]. Closely related family members are often the most effective allogeneic donors because their immune systems are the most similar to the recipients [1, 4].…”

“…Allogeneic transplants differ in that stem cells are harvested from a donor (with similar immune system markers to the recipient) and transplanted to the recipient [1, 4]. Closely related family members are often the most effective allogeneic donors because their immune systems are the most similar to the recipients [1, 4]. Xenogeneic transplants are similar to allogeneic transplants in that there is a mismatch in the donor and the recipient, but xenogeneic transplants involve a donor of a different species than the recipient [1, 4].…”