Almost two years ago, a team led by a Detroit pediatric researcher helped prove that hypothermia (brain cooling) treatment can significantly reduce death and physical and mental disability that is caused by reduced oxygen and blood flow in the brain. When a term baby receives hypothermia treatment within 6 hours after suffering a brain injury caused by oxygen deprivation (called hypoxic ischemic encephalopathy (HIE)), the baby’s chances of dying or having permanent brain damage are significantly reduced. In other words, if HIE occurs in a baby, the HIE is much less likely to cause death and cerebral palsy if the baby is given brain cooling treatment right away.
The leader of this groundbreaking study, Dr. Seetha Shankaran of Wayne State University / Detroit Medical Center, worked with the National Institute of Child Health and Human Development (NICHD) to prove that hypothermia treatment can decrease and prevent brain damage and death in babies. Thanks to Dr. Shankaran’s 10+ years of work studying brain cooling, hypothermia treatment is now that standard of care in most hospitals around the world for babies with HIE.
More recently, researchers at WSU / DMC have found a way to improve movement disorders in rabbits that have cerebral palsy by using nanotechnology to deliver drugs to the rabbits’ brains. Nanotechnology is a technology that involves very small supramolecules that are often the size of atoms. The nano-devices developed by these researchers can carry medicine to the specific part of the brain involved in cerebral palsy. The findings suggest that there is an opportunity to deliver drug treatment to a baby’s brain right after birth (or even in-utero) to minimize the effects of cerebral palsy. Dr. Roberto Romero, a chief investigator on the study said, “There is new hope to prevent a disorder that has been considered incurable – Cerebral Palsy.”
These nano-devices will hopefully be able to aid in the diagnosis and treatment of all inflammatory processes in the brain, including infections in a baby’s brain that can cause cerebral palsy.
The researchers are collaborating with researchers from the National Institute of Health (NIH) to fully develop nanotechnology for prevention and treatment of maternal infections and fetal brain injury, and the team’s hope is that their approach may one day eliminate or decrease the occurrence of cerebral palsy.
According to the research team, their results are the first to show that dendrimers (a type of molecule) are able to target the specific site of injury in the brain when brain inflammation is present. Using this nano-therapeutic approach, the targeted drugs are 10 to 100 times more effective than drugs given through an IV.
“There is an increasing body of literature, in addition to evidence from our own research relating to the disease mechanisms, that suggests that neuron-inflammation [brain inflammation] plays a key role in the pathogenesis and evolution of cerebral palsy and other diseases,” says Rangaramanujam Kannan, one of the study’s researchers. “We hope to develop therapeutic approaches that will target and treat neuron-inflammation resulting in significantly improved treatment outcomes.”
A wide variety of brain diseases are very difficult to treat due to lack of technology able to target the affected areas in the brain and central nervous system. “We believe that our novel drug-carrying nanodevice will offer solutions for treatment of such conditions by delivering drugs to the specific target,” Kannan adds.
Inflammation in the brain can be detected almost as soon as it begins. Sujatha Kannan has established an animal model of inflammation that mimics cerebral palsy. She and her team have shown that the presence of brain inflammation can be detected at a very early stage using a brain scan called Positron Emission Tomography, which is a noninvasive way to take pictures of the brain. Clinical studies for the detection of brain inflammation in at-risk newborns are currently underway.
“The PRB has established a unit to develop applications of nanotechnology in perinatal medicine under the leadership of Dr. R. Kannan because we are convinced that this approach will enhance early diagnosis of inflammation in utero as well as treatment,” says Dr. Robert Romero. “Sujatha Kannan and R. Kannan have explored potential mechanisms to prevent and treat inflammation-induced cerebral palsy. Application to humans requires new methods for diagnosis and drug delivery into the amniotic cavity. Such goals could be accomplished using nanotechnology and, hence, the partnership between Dr. Kannan and the Perinatology Research Branch,” Romero adds.
The PRB nanotechnology lab now has six postdoctoral researchers and two graduate students with broad research expertise ranging from chemistry, engineering, neuroscience, pharmacology, cell biology, animal model development and imaging. The team of researchers is led by Rangaramanujam Kannan, professor of chemical engineering, with collaborators Dr. Sujatha Kannan, assistant professor of pediatrics in the School of Medicine and Dr. Romero, chief of the NICHD’s Perinatology Research Branch (PRB) at the Detroit Medical Center.
As many as four out every 1,000 babies worldwide are born with cerebral palsy. It is a condition that affects brain development and leaves children struggling with movement and coordination.
Cerebral palsy is a chronic childhood condition that can be caused by many different events. Injury to the developing brain that occurs near or during the time of labor and delivery can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. The following conditions can cause cerebral palsy:
- HIE, which is caused by oxygen deprivation in the brain, including a lack of blood flow in the brain from a stroke or brain bleed. Oxygen deprivation can be caused by conditions such as uterine rupture, umbilical cord prolapse, placental abruption, and failure to perform a timely C-section when the baby is in distress.
- Untreated high bilirubin levels in a newborn (jaundice), which can cause a form of brain damage called kernicterus.
- Brain infection in the baby, which can be caused by untreated or improperly treated infections in the mother, such as Group B Strep (GBS), urinary tract infection (UTI), bacterial vaginosis (BV), herpes simplex virus (HSV) and chorioamnionitis.
CEREBRAL PALSY AND MEDICAL MALPRACTICE
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