Cerebrovascular diseases are the fourth leading cause of death in Japan. Among them, cerebral infarction, in which blood flow to the brain is interrupted and tissue necrosis is induced, often interferes with daily life due to its aftereffects. Rehabilitation plays a vital role in restoring functions damaged by cerebral infarction.
 Natsumi Yamaguchi, a third-year doctoral student in the Graduate School of Life Sciences, is researching the mechanisms of rehabilitation for functional recovery after cerebral infarction. We spoke to Yamaguchi, who has been pursuing her research day and night based on a question she has been asking herself since she was a child.

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Working to elucidate the mechanisms of rehabilitation for functional recovery

 First, let's get the facts straight about cerebrovascular diseases. Stroke is a cerebrovascular disease that we often hear about, but it can be divided into three different conditions: cerebral hemorrhage, subarachnoid hemorrhage, and cerebral infarction. Cerebral hemorrhage is a condition in which a small blood vessel in the brain breaks for some reason, causing bleeding in the brain, while subarachnoid hemorrhage is a condition in which an aneurysm or arteriovenous malformation in a large blood vessel feeding the brain ruptures, causing bleeding on the surface of the brain. And finally, cerebral infarction occurs when blood vessels in the brain suddenly become blocked, interrupting blood flow and causing necrosis of brain tissue.
 The central nervous system, which consists of the brain and spinal cord, has little regenerative capacity, and when this system is damaged and its functionality is lost, patients are left with aftereffects such as motor paralysis, sensory impairment, higher brain dysfunction, and impaired consciousness.
 By using C.B-17/lcr-+/+Jcl lab mice, Yamaguchi is focusing on the surviving brain regions adjacent to where the cerebral infarction occurred and is working to clarify the mechanisms by which exercise, one of the core elements of rehabilitation, promotes the functional recovery.
 “C.B-17/lcr-+/+Jcl mice are characterized by very small individual differences in their vascular structures. The ability to induce cerebral infarctions of the same size in the same location in any individual mouse makes it possible to accurately compare and evaluate even minute changes caused by exercise. Thus far, there have only been a few cases in which these lab mice have been used to study the recovery mechanisms of rehabilitation, so this is the strength of my research,” explains Yamaguchi.
 This research revealed that when functional recovery is accelerated by exercise after cerebral infarction, the decrease in the number of dendritic spines, which are essential for neuronal activity, is ameliorated in the motor regions adjacent to the infarction, and that astrocytes, one of the glial cells that support the network and function of neurons, remain abundant in the region. Because these changes are minute, they have been hidden by individual differences and have been difficult to detect until now, but Yamaguchi's research has paved the way for a more accurate understanding of them. Currently, she is trying to elucidate the changes in astrocyte function induced by exercise and the effect this has on ameliorating dendritic spine loss and promoting functional recovery.

Embracing interests from childhood

 Yamaguchi says that her research into the mechanisms of functional recovery by way of rehabilitation was triggered by a TV program she saw when she was in junior high school.
 "When I saw someone on a TV show regaining function through serious rehabilitation, I thought, ' Why the functional recovery is promoted even though neurons have limited capacity for regeneration?’ I can recall very clearly that I found this extremely interesting even as a child. I continue to pursue this interest to this day,” says Yamaguchi.
 Since childhood, Yamaguchi says she has always been curious and interested in things she didn’t understand and that made her wonder “why,” and she has always been willing to face these questions head-on. She harnessed her inherent proactive nature to help improve the research environment related to cerebral infarction and rehabilitation in the laboratory.
 “In the lab I belong to, we are currently working to observe and elucidate the structure of the brain, its functions, pathologies, and the nature of nerve cells. Until I became a graduate student, however, the aftereffects of cerebral infarction and recovery mechanisms driven by rehabilitation had never really been researched. Still, I have wanted to do serious laboratory research based on my childhood interests ever since I was an undergraduate student; therefore, I figured I should learn what I need to know to conduct this kind of research so I could do it in my current laboratory. I worked hard to learn what research equipment I would need by visiting outside research institutions," explains Yamaguchi.


Remaining unemotional in the face of research findings

 There is one important thing that Yamaguchi keeps in mind when conducting her research: remaining unemotional in the face of research findings. Regardless of whether the results of the experiment are good or bad, she accepts them without hesitation and tries to move forward.
 “In my laboratory, as a condition for completing the second semester of the doctoral program, you must have multiple acceptances in overseas peer-reviewed journals. To get a paper accepted, it must be novel and have multiple experimental results to support the hypothesis. Even if I end up with an unexpected experimental result, I try to unemotionally analyze why the result was obtained and then link that to the next step I need to take. Conversely, even if the results meet my expectations, I try to logically construct the facts obtained without being overly pleased. To face research findings seriously, I think it is important to always keep emotions out of the equation,” says Yamaguchi.
 The world of academia these days is a demanding environment that requires researchers to produce a large volume of research output in a short period of time. This is why we see and hear in the press stories of researchers who, in their haste and desire to produce good results, engage in research and publication misconduct. Yamaguchi takes a matter-of-fact approach to her work while harboring a passion for research because she continues to genuinely value the interests that drive her. Just by talking to her, we could sense her strong will.


The joy of working with people from various fields and moving to a new stage

 Yamaguchi has been selected as a RARA Student Fellow. RARA Student Fellows are expected to become the next generation of researchers who combine international sensibility, interdisciplinarity, and a multifaceted approach as they improve their individual research skills and interact with researchers from different fields both in Japan and overseas.
 “Before becoming a RARA Student Fellow, I had very few opportunities to interact with researchers in other fields. However, I now have regular opportunities to communicate with graduate students in other fields. They ask me a lot of questions from angles I had never considered before, and I am putting this into practice in my research now. I often receive novel questions from graduate students in science fields other than the life sciences, and this helps me to constantly approach my research with a fresh mindset," says Yamaguchi.
 By engaging in friendly competition with graduate students from different fields, Yamaguchi has gained a broader perspective and has even received a job offer to work as a researcher in a company.
 “Honestly, hunting for a job while working on my PhD was hard. Since you cannot suspend your research activities to just concentrate on the job search, you need to strike a good balance between the two. That being said, I am very happy to have found a research position at the company I wanted to work for. As a researcher at a company, I would like to make use of the skills and experience I have cultivated so far and introduce a wide array of products into the world," remarks Yamaguchi.
 Finally, when we asked Yamaguchi about what she finds appealing about research, she responded as only she could.
 “When you look at the morphology of neurons, it's really beautiful. More than obtaining good results, when I am able to visualize and observe something that you cannot normally see, it makes me think I am glad to be a researcher.
 Embracing an interest that she has held since childhood, Yamaguchi has been earnestly engaged in research and will surely continue to tackle new challenges in the future.


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